铅镉联合对新生大鼠中枢神经系统的毒性损伤及NAC保护效应的研究
|
摘要
近年来,对环境化学物毒性危害的研究已由原来单一因素为主向因素间联合作用方向发展。铅、镉均是生产和生活中接触频率大、暴露范围广的蓄积性毒物,能对发育中的中枢神经系统产生重要影响。铅、镉单独作用的报道较多,而对两者的联合毒性研究则相对较少,尤其是铅镉联合对处于发育早期的动物中枢神经系统毒性损伤的系统研究较为罕见。本研究选用新生大鼠作为试验动物,通过体外和体内实验相结合的方法较系统的探讨了铅、镉及其联合对新生大鼠中枢神经系统的毒性损伤效应及其可能的作用机理,为进一步认识铅、镉及其联合毒性作用提供理论依据。
一、体外试验选用新生24h内SD大鼠作为试验用神经细胞的来源,采用尼氏染色对皮质神经细胞进行了形态鉴定和纯度分析,用CCK-8法检测了一个生长周期内神经细胞的活性分布,成功建立了大脑皮质神经细胞毒性试验的体外培养模型:在此基础上,在培养液中添加不同浓度的Pb、Cd,共分9组,分别为对照组、P_1(Pb100μmol/L)、P_2(Pb 200μmol/L)、C_1(Cd 5μmol/L)、C_2(Cd 10μmol/L)、P_1C_1(Pb100μmol/L+Cd 5μmol/L)、P_1C_2(Pb 100μmol/L+Cd 10μmol/L)、P_2C_1(Pb 200μmol/L+Cd 5μmol/L)、P_2C_2(Pb 200μmol/L+Cd 10μmol/L)组。分别从神经细胞形态学、神经细胞存活率、神经细胞凋亡率以及神经细胞GSH-Px、SOD、CAT、TChE活性和MDA含量等方面对铅、镉损伤新生大鼠大脑皮质神经细胞进行了研究;同时,添加N-乙酰半胱氨酸(NAC),观察其在铅镉损伤神经细胞过程中的保护效果。结果表明,①本试验培养的大脑皮质神经细胞,经尼氏染色鉴定并计数神经细胞纯度在92%以上,且在一个生长周期内培养至第6d时神经细胞的OD值最高,因此,本试验将第6d确定为铅镉处理神经细胞的时间;②与对照组相比,铅、镉及其联合均能导致神经细胞数量减少、网络减少或消失;能使胞体短直径和突起长度显著变小和缩短(P＜0.05);使神经细胞的存活率显著下降(P＜0.05),且具有明显的时间与剂量效应;各染毒组神经细胞核皱缩、呈新月形、染色质致密浓染,甚至出现核碎裂,细胞凋亡率显著升高(P＜0.05);与相应单独染毒组比较,各联合染毒组上述指标变化更为严重,P_1C_2组较P_2C_1组改变明显,其中以P_2C_2组最为显著(P＜0.05);③与对照组比较,各染毒组神经细胞GSH-Px、SOD、TChE活性均显著下降(P＜0.05),而CAT活性和MDA含量则显著升高(P＜0.05);④在NAC拮抗铅、镉及其联合毒性试验中,可以看出NAC能使神经细胞存活率升高、细胞凋亡率下降,能使GSH-Px、SOD、TChE、CAT活性升高及MDA含量下降,但无显著性差异(P＞0.05)。由上述试验结果可以得出以下结论:①铅、镉及其联合能使神经细胞胞体变小,神经细胞突起变短,神经细胞间网络连接减少;能使神经细胞存活率下降,神经细胞凋亡率增加,且具有明显的时间和剂量效应。铅镉联合表现协同毒性效应,其中镉在联合作用中发挥主导作用;②铅、镉及其联合能显著改变神经细胞GSH-Px、SOD、CAT、TChE活性和MDA含量,因此,铅、镉的神经系统毒性与其脂质过氧化损伤有关;③添加NAC可以提高神经细胞的存活率,减少凋亡细胞的数量,增加GSH-Px、SOD、CAT、TChE活性,减少MDA的生成,说明NAC具有一定的拮抗铅、镉毒性损伤的作用,但保护效果不明显。
二、体内试验35只怀孕母鼠被随机分为7组,分别为对照组(饮用蒸馏水)、铅组(300mg/L)、铅+NAC组(300mg/L+20mmol/L)、镉组(10mg/L)、镉+NAC组(10mg/L+20mmol/L)、铅镉联合组(300mg/L+10mg/L)、铅镉联合+NAC组(300mg/L+10mg/L+20mmol/L)。经饮水染毒,染毒时间为整个妊娠期,待分娩后观察并记录:①铅、镉及其联合对新生鼠生长发育的影响;②用光学显微镜、透射电子显微镜观察新生鼠大脑皮质组织病理学及超微结构的变化;③测定新生鼠脑组织GSH-Px、SOD、CAT、TChE活性及MDA含量;④ICP-MS检测了新生鼠体内主要微量元素Cu、Fe、Zn、Mn及Se含量;⑤FQ-PCR法检测了凋亡基因bcl-2、Bax和c-fos在新生鼠大脑皮质中的表达;免疫组织化学和FQ-PCR法检测了MT-3在新生鼠大脑皮质中的表达研究;⑥同时进行了相关指标的NAC保护试验研究。结果表明,①与对照组比较,各染毒组新生鼠体重和脑重均明显下降(P＜0.05或P＞0.05),其中以铅镉联合组降低最为明显;②新生鼠大脑皮质组织经HE染色未见明显异常的病理组织学变化,但超微结构变化明显,表现神经细胞核固缩、变形,染色质边聚、轻度溶解,线粒体肿胀、嵴部分或完全消失,铅镉联合对新生鼠大脑皮质超微结构的损伤较铅、镉单独时严重;③各染毒组新生鼠体内微量元素Cu、Fe、Zn、Mn和Se含量均显著低于对照组(P＜0.05),以铅镉联合组降低最为明显;④与对照组相比,铅、镉及其联合均使新生鼠脑组织GSH-Px、SOD、TChE、CAT活性下降及MDA含量升高(P＜0.05或P＞0.05);⑤各染毒组新生鼠大脑皮质bcl-2基因的表达均低于对照组(P＜0.05或P＞0.05),而Bax、c-fos和MT-3表达则显著高于对照组(P＜0.05);⑥NAC保护组与相应染毒组比较,新生鼠体内微量元素Cu、Fe、Zn、Mn和Se含量均有所升高(P＜0.05或P＞0.05),脑组织GSH-Px、SOD、TChE、CAT活性均有不同程度升高但差异不显著(P＞0.05),MDA含量则显著下降(P＜0.05),大脑皮质bcl-2基因的表达量明显增加(P＜0.05或P＞0.05),而Bax和c-fos表达则显著减少(P＜0.05)。通过对本部分试验结果的分析,可得出以下结论:①母鼠妊娠期铅、镉及其联合暴露能明显减轻新生鼠体重和脑重,导致新生鼠脑发育迟缓;②母鼠妊娠期铅、镉及其联合暴露对新生鼠大脑皮质超微结构有显著影响,导致细胞膜破裂,细胞核固缩、变形,线粒体肿胀、嵴部分或完全消失;③铅、镉及其联合导致机体抗氧化酶活性降低可能与其微量元素Cu、Fe、Zn、Mn和Se含量下降有关;④铅、镉及其联合诱导神经细胞凋亡与bcl-2、Bax、c-fos基因的异常表达有关,铅镉联合表现协同毒性效应;⑤母鼠妊娠期铅、镉及其联合暴露的同时添加NAC可以提高新生鼠体重和脑重,新生鼠体内微量元素的含量增加,使新生鼠脑组织内GSH-Px、SOD、CAT、TChE活性升高,MDA含量显著降低,能增加bcl-2的表达量、减少Bax、c-fos和MT-3的表达量,表明NAC对铅、镉毒性损伤具有一定的保护作用。
In recent years,the trend of studies on environmental chemical toxic substances is from the previous single factor to the present combined ones.Lead(Pb) and cadmium(Cd) are known as toxicants which are accumulative,large-contact frequent,extensive exposure in daily life.Lead and cadmium have deep influences upon the developmenting central nervous system(CNS).The studies on single toxicity of cadmium or lead are reported in many documents.However,systemic studies of toxic damage on combination of lead and cadmium are seldom seen,especially in developmenting CNS.This study aims to investigate the toxic effects and mechanism of lead or/and cadmium on CNS of neonatal rats(in 24h) in vitro and in vivo,which will probably offer some theoretic evidence of further acquiring neurotoxicity mechanism of lead or/and cadmium.
1.Experiments in vitro To study lead and/or cadmium neurotoxicity mechanism on CNS,the experimental neurons are obtained from the neonatal Sprague-Dawley rats in 24h.The model of neurons in vitro is successfully established,which is proved by adopting the Nissl's staining,CCK-8 assay methods.The toxic tests of lead and/or cadmium are divided into 9 groups:the control group,P_1 group(Pb 100μmol/L)、P_2 group (Pb 200μmol/L)、C_1 group(Cd 5μmol/L)、C_2 group(Cd 10μmol/L)、P_1C_1 group(Pb 100μmol/L+Cd 5μmol/L)、P_1C_2 group(Pb 100μmol/L+Cd 10μmol/L)、P_2C_1 group(Pb 200μmol/L+Cd 5μmol/L)、P_2C_2 group(Pb 200μmol/L+Cd 10μmol/L).The toxic effect of lead and/or cadmium on neuron's morphology,viability,apoptosis rate,the enzymatic activity changes of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD), catalase(CAT) and True choline esterase(TChE) and the contents of Maleic dialdehyde (MDA) are evaluated by related kits.Meanwhile,N-Acetylcysteine(NAC) is added in each experimental group to study the protective effects from the damages of lead and/or cadmium.The results are as follows:①The results of Nissl's staining shows that the purity of neurons is above 92%,and the cortical neuron's viability(OD)is highest on the sixth day of post-beginning of culturing.So neurons are treated the with experimental factors on the sixth day;②In comparison with the control group,the neurons are exposed to different concentrations of lead or/and cadmium,which led to the decrease in the number of neurons and neural network.The results indicated a significant decrease in pericaryons and processes(p＜0.05),and survival rate of neurons(p＜0.05).And the inhibitory effect is gradually enhanced with the prolonging of the culturing time and increasing concentrations of lead or/and cadmium.The nucleus crimpled,crescent liked and chromatin condensed,even nucleus disintegrated by the fluorescence microscope. And apoptosis rate is higher than the control group(P＜0.05);In comparison with the single factor treats groups respectively,the combined factors groups have more significant changes,such as between P_1C_2 and P_2C_1,especially in P_2C_2 group(P＜0.05);③In comparison with the control group,the activities of GSH-Px,SOD and TChE in neurons which are treated by lead or/and cadmium of different concentrations decrease significantly(P＜0.05).However,the activity of CAT and the content of MDA in neurons are more significantly increased than that of the control group(P＜0.05);④To compare the NAC protective groups with the poisoning groups,the neuron's viability was increased,and the apoptosis rate of neurons was degraded relative to the poisoning groups. Meanwhile,the activities of GSH-Px,SOD,TChE and CAT are increased accordingly, but the content of MDA is decreased compared with the poisoning groups.However, there are no significant changes among the relative groups(P＞0.05).From what has been discussed above,it might be concluded that:①The cortical neuron differentiation can be inhibited by lead or/and cadmium,which led to the pericaryon diminutus and process decurtation,lower survival rate and higher apoptosis rate and displays a dose and time effect in comparison with the control group.It is clear that lead and cadmium combined treatment exerts an synergistic effect,and cadmium played a great role in combining lead with cadmium;②The antioxidative enzyme activity of GSH-Px,SOD,CAT,TChE and content of MDA are significantly changed in each of experimental groups.Therefore, Nervous system toxicity of lead and/or cadmium is connected with lipid peroxidation;③The toxicity of lead or/and cadmium could antagonize by adding NAC,which improve survival rate of neurons and reduce apoptosis rate of neurons and increase activity of antioxidase and reduce lipid peroxidation.It is not obvious that adding NAC has a protective effects on the damage of lead or/and cadmium.
2.Experiments in vivo To set up experimental animal mode of the damage Pb or/and Cd exposed in neonatal SD rats,35 SD pregnancy rats are used from the center of experimental animal of Yangzhou University,and are randomly divided into 7 groups:the control group(drinking water),lead acetate group(300mg/L),lead acetate+NAC(300 mg/L+20mmol/L),cadmium acetate group(10mg/L),cadmium acetate+NAC (10mg/L+20mmol/L),group of lead and cadmium(300mg/L+10mg/L),group of lead and cadmium+NAC(300mg/L+10mg/L+20mmol/L),which are given by drinking water during gestational periods.After delivery,neonatal SD rats are used to examine the toxic effects of lead or/and cadmium and appraise protective effect of NAC.Experimental examination index was that①Toxic effect of lead and/or cadmium on physical growth (such as body weight,brain weight) and development of brain;②The studies on the changes in histopathology and ultrastructure of cerebral cortex of the neonatal SD rats;③Toxic effects of lead or/and cadmium on the biochemistry index of neonatal rats brain, such as the activity of GSH-Px,SOD,CAT and TChE and the content of MDA;④Effect of lead or/and cadmium on contents of trace element(Cu,Fe,Zn,Mn and Se) in neonatal rats;⑤The expression of bcl-2,Bax,c-fos in the cerebral cortex by FQ-PCR and MT-3 by FQ-PCR and immunohistochemistry method;⑥The protective effects of NAC on damage of lead or/and cadmium in developing brain of neonatal rats.The results are as follows:①In comparison with the control group,the body weight and brain weight are obviously decreased in lead or/and cadmium group(P＜0.05 or P＞0.05), especially in the combination group;②The changes in histopathology of cerebral cortex is not observed under light microscope.However,the changes in ultrastructure of cerebral cortex is obvious that pyknosis of neuron nucleus,chromatin assemble,mitochondrial swelling and partial cristae under transmission electronic microscope;③In each of experimental groups,the activities of GSH-Px,SOD,CAT and TChE are significantly decreased than those in the normal group(P＜0.05),however,the content of MDA is significantly increased in the experimental group than that in the normal group(P＜0.05);④In the poisoning groups,the contents of trace element(Cu、Fe、Zn、Mn and Se) descend more significantly than the normal group(P＜0.05);⑤In comparison with control group,the expression of bcl-2 in the cerebral cortex decrease(P＜0.05 or P＞0.05),but the expression of Bax,c-fos and MT-3 increase in the experimental groups(P＜0.05 or P＞0.05);⑥In comparison with the poisoning groups respectively,the protective groups of NAC are not only contents of trace element(Cu,Fe,Zn,Mn and Se) are improved,but also the activity of GSH-Px,SOD,CAT and TChE are higher(P＞0.05)and the content of MDA is significantly lower(P＜0.05).The expression levels of bcl-2 in the cerebral cortex is obviously increased(P＜0.05 or P＞0.05),but the expression levels of Bax and c-fos are significantly decreased in the experimental group(P＜0.05).The conclusions drawn by analyzing the test results are as following:①The body weight and brain weight of neonatal rats are significantly decreased by lead or/and cadmium exposed to gestational rats;②There are obvious changes in ultrastructure of the cerebral cortex which displayed as cytomembrane disappearance and neuron nucelus concentration,mitochondrial swelling,disruption and total cristae loss;③The reducing activity of antioxidase led to lead or/and cadmium could be related to the decreasing contents of trace element in neonatal rats;④The apoptosis of neurons induced by lead or/and cadmium are in connection with the exceptional expression of bcl-2、Bax and c-fos genes.It is clear that lead and cadmium combined treatment exerts an synergistic effect;⑤NAC,as a new-style antioxidant,could antagonize toxicity of lead or/and cadmium, which improves activity of antioxidase and reducing lipid peroxidation and increasing content of trace element and increasing gene expression of bcl-2 and decreasing gene expression of Bax、c-fos and MT-3,while its protective effect was limited.
一、体外试验选用新生24h内SD大鼠作为试验用神经细胞的来源,采用尼氏染色对皮质神经细胞进行了形态鉴定和纯度分析,用CCK-8法检测了一个生长周期内神经细胞的活性分布,成功建立了大脑皮质神经细胞毒性试验的体外培养模型:在此基础上,在培养液中添加不同浓度的Pb、Cd,共分9组,分别为对照组、P_1(Pb100μmol/L)、P_2(Pb 200μmol/L)、C_1(Cd 5μmol/L)、C_2(Cd 10μmol/L)、P_1C_1(Pb100μmol/L+Cd 5μmol/L)、P_1C_2(Pb 100μmol/L+Cd 10μmol/L)、P_2C_1(Pb 200μmol/L+Cd 5μmol/L)、P_2C_2(Pb 200μmol/L+Cd 10μmol/L)组。分别从神经细胞形态学、神经细胞存活率、神经细胞凋亡率以及神经细胞GSH-Px、SOD、CAT、TChE活性和MDA含量等方面对铅、镉损伤新生大鼠大脑皮质神经细胞进行了研究;同时,添加N-乙酰半胱氨酸(NAC),观察其在铅镉损伤神经细胞过程中的保护效果。结果表明,①本试验培养的大脑皮质神经细胞,经尼氏染色鉴定并计数神经细胞纯度在92%以上,且在一个生长周期内培养至第6d时神经细胞的OD值最高,因此,本试验将第6d确定为铅镉处理神经细胞的时间;②与对照组相比,铅、镉及其联合均能导致神经细胞数量减少、网络减少或消失;能使胞体短直径和突起长度显著变小和缩短(P＜0.05);使神经细胞的存活率显著下降(P＜0.05),且具有明显的时间与剂量效应;各染毒组神经细胞核皱缩、呈新月形、染色质致密浓染,甚至出现核碎裂,细胞凋亡率显著升高(P＜0.05);与相应单独染毒组比较,各联合染毒组上述指标变化更为严重,P_1C_2组较P_2C_1组改变明显,其中以P_2C_2组最为显著(P＜0.05);③与对照组比较,各染毒组神经细胞GSH-Px、SOD、TChE活性均显著下降(P＜0.05),而CAT活性和MDA含量则显著升高(P＜0.05);④在NAC拮抗铅、镉及其联合毒性试验中,可以看出NAC能使神经细胞存活率升高、细胞凋亡率下降,能使GSH-Px、SOD、TChE、CAT活性升高及MDA含量下降,但无显著性差异(P＞0.05)。由上述试验结果可以得出以下结论:①铅、镉及其联合能使神经细胞胞体变小,神经细胞突起变短,神经细胞间网络连接减少;能使神经细胞存活率下降,神经细胞凋亡率增加,且具有明显的时间和剂量效应。铅镉联合表现协同毒性效应,其中镉在联合作用中发挥主导作用;②铅、镉及其联合能显著改变神经细胞GSH-Px、SOD、CAT、TChE活性和MDA含量,因此,铅、镉的神经系统毒性与其脂质过氧化损伤有关;③添加NAC可以提高神经细胞的存活率,减少凋亡细胞的数量,增加GSH-Px、SOD、CAT、TChE活性,减少MDA的生成,说明NAC具有一定的拮抗铅、镉毒性损伤的作用,但保护效果不明显。
二、体内试验35只怀孕母鼠被随机分为7组,分别为对照组(饮用蒸馏水)、铅组(300mg/L)、铅+NAC组(300mg/L+20mmol/L)、镉组(10mg/L)、镉+NAC组(10mg/L+20mmol/L)、铅镉联合组(300mg/L+10mg/L)、铅镉联合+NAC组(300mg/L+10mg/L+20mmol/L)。经饮水染毒,染毒时间为整个妊娠期,待分娩后观察并记录:①铅、镉及其联合对新生鼠生长发育的影响;②用光学显微镜、透射电子显微镜观察新生鼠大脑皮质组织病理学及超微结构的变化;③测定新生鼠脑组织GSH-Px、SOD、CAT、TChE活性及MDA含量;④ICP-MS检测了新生鼠体内主要微量元素Cu、Fe、Zn、Mn及Se含量;⑤FQ-PCR法检测了凋亡基因bcl-2、Bax和c-fos在新生鼠大脑皮质中的表达;免疫组织化学和FQ-PCR法检测了MT-3在新生鼠大脑皮质中的表达研究;⑥同时进行了相关指标的NAC保护试验研究。结果表明,①与对照组比较,各染毒组新生鼠体重和脑重均明显下降(P＜0.05或P＞0.05),其中以铅镉联合组降低最为明显;②新生鼠大脑皮质组织经HE染色未见明显异常的病理组织学变化,但超微结构变化明显,表现神经细胞核固缩、变形,染色质边聚、轻度溶解,线粒体肿胀、嵴部分或完全消失,铅镉联合对新生鼠大脑皮质超微结构的损伤较铅、镉单独时严重;③各染毒组新生鼠体内微量元素Cu、Fe、Zn、Mn和Se含量均显著低于对照组(P＜0.05),以铅镉联合组降低最为明显;④与对照组相比,铅、镉及其联合均使新生鼠脑组织GSH-Px、SOD、TChE、CAT活性下降及MDA含量升高(P＜0.05或P＞0.05);⑤各染毒组新生鼠大脑皮质bcl-2基因的表达均低于对照组(P＜0.05或P＞0.05),而Bax、c-fos和MT-3表达则显著高于对照组(P＜0.05);⑥NAC保护组与相应染毒组比较,新生鼠体内微量元素Cu、Fe、Zn、Mn和Se含量均有所升高(P＜0.05或P＞0.05),脑组织GSH-Px、SOD、TChE、CAT活性均有不同程度升高但差异不显著(P＞0.05),MDA含量则显著下降(P＜0.05),大脑皮质bcl-2基因的表达量明显增加(P＜0.05或P＞0.05),而Bax和c-fos表达则显著减少(P＜0.05)。通过对本部分试验结果的分析,可得出以下结论:①母鼠妊娠期铅、镉及其联合暴露能明显减轻新生鼠体重和脑重,导致新生鼠脑发育迟缓;②母鼠妊娠期铅、镉及其联合暴露对新生鼠大脑皮质超微结构有显著影响,导致细胞膜破裂,细胞核固缩、变形,线粒体肿胀、嵴部分或完全消失;③铅、镉及其联合导致机体抗氧化酶活性降低可能与其微量元素Cu、Fe、Zn、Mn和Se含量下降有关;④铅、镉及其联合诱导神经细胞凋亡与bcl-2、Bax、c-fos基因的异常表达有关,铅镉联合表现协同毒性效应;⑤母鼠妊娠期铅、镉及其联合暴露的同时添加NAC可以提高新生鼠体重和脑重,新生鼠体内微量元素的含量增加,使新生鼠脑组织内GSH-Px、SOD、CAT、TChE活性升高,MDA含量显著降低,能增加bcl-2的表达量、减少Bax、c-fos和MT-3的表达量,表明NAC对铅、镉毒性损伤具有一定的保护作用。
In recent years,the trend of studies on environmental chemical toxic substances is from the previous single factor to the present combined ones.Lead(Pb) and cadmium(Cd) are known as toxicants which are accumulative,large-contact frequent,extensive exposure in daily life.Lead and cadmium have deep influences upon the developmenting central nervous system(CNS).The studies on single toxicity of cadmium or lead are reported in many documents.However,systemic studies of toxic damage on combination of lead and cadmium are seldom seen,especially in developmenting CNS.This study aims to investigate the toxic effects and mechanism of lead or/and cadmium on CNS of neonatal rats(in 24h) in vitro and in vivo,which will probably offer some theoretic evidence of further acquiring neurotoxicity mechanism of lead or/and cadmium.
1.Experiments in vitro To study lead and/or cadmium neurotoxicity mechanism on CNS,the experimental neurons are obtained from the neonatal Sprague-Dawley rats in 24h.The model of neurons in vitro is successfully established,which is proved by adopting the Nissl's staining,CCK-8 assay methods.The toxic tests of lead and/or cadmium are divided into 9 groups:the control group,P_1 group(Pb 100μmol/L)、P_2 group (Pb 200μmol/L)、C_1 group(Cd 5μmol/L)、C_2 group(Cd 10μmol/L)、P_1C_1 group(Pb 100μmol/L+Cd 5μmol/L)、P_1C_2 group(Pb 100μmol/L+Cd 10μmol/L)、P_2C_1 group(Pb 200μmol/L+Cd 5μmol/L)、P_2C_2 group(Pb 200μmol/L+Cd 10μmol/L).The toxic effect of lead and/or cadmium on neuron's morphology,viability,apoptosis rate,the enzymatic activity changes of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD), catalase(CAT) and True choline esterase(TChE) and the contents of Maleic dialdehyde (MDA) are evaluated by related kits.Meanwhile,N-Acetylcysteine(NAC) is added in each experimental group to study the protective effects from the damages of lead and/or cadmium.The results are as follows:①The results of Nissl's staining shows that the purity of neurons is above 92%,and the cortical neuron's viability(OD)is highest on the sixth day of post-beginning of culturing.So neurons are treated the with experimental factors on the sixth day;②In comparison with the control group,the neurons are exposed to different concentrations of lead or/and cadmium,which led to the decrease in the number of neurons and neural network.The results indicated a significant decrease in pericaryons and processes(p＜0.05),and survival rate of neurons(p＜0.05).And the inhibitory effect is gradually enhanced with the prolonging of the culturing time and increasing concentrations of lead or/and cadmium.The nucleus crimpled,crescent liked and chromatin condensed,even nucleus disintegrated by the fluorescence microscope. And apoptosis rate is higher than the control group(P＜0.05);In comparison with the single factor treats groups respectively,the combined factors groups have more significant changes,such as between P_1C_2 and P_2C_1,especially in P_2C_2 group(P＜0.05);③In comparison with the control group,the activities of GSH-Px,SOD and TChE in neurons which are treated by lead or/and cadmium of different concentrations decrease significantly(P＜0.05).However,the activity of CAT and the content of MDA in neurons are more significantly increased than that of the control group(P＜0.05);④To compare the NAC protective groups with the poisoning groups,the neuron's viability was increased,and the apoptosis rate of neurons was degraded relative to the poisoning groups. Meanwhile,the activities of GSH-Px,SOD,TChE and CAT are increased accordingly, but the content of MDA is decreased compared with the poisoning groups.However, there are no significant changes among the relative groups(P＞0.05).From what has been discussed above,it might be concluded that:①The cortical neuron differentiation can be inhibited by lead or/and cadmium,which led to the pericaryon diminutus and process decurtation,lower survival rate and higher apoptosis rate and displays a dose and time effect in comparison with the control group.It is clear that lead and cadmium combined treatment exerts an synergistic effect,and cadmium played a great role in combining lead with cadmium;②The antioxidative enzyme activity of GSH-Px,SOD,CAT,TChE and content of MDA are significantly changed in each of experimental groups.Therefore, Nervous system toxicity of lead and/or cadmium is connected with lipid peroxidation;③The toxicity of lead or/and cadmium could antagonize by adding NAC,which improve survival rate of neurons and reduce apoptosis rate of neurons and increase activity of antioxidase and reduce lipid peroxidation.It is not obvious that adding NAC has a protective effects on the damage of lead or/and cadmium.
2.Experiments in vivo To set up experimental animal mode of the damage Pb or/and Cd exposed in neonatal SD rats,35 SD pregnancy rats are used from the center of experimental animal of Yangzhou University,and are randomly divided into 7 groups:the control group(drinking water),lead acetate group(300mg/L),lead acetate+NAC(300 mg/L+20mmol/L),cadmium acetate group(10mg/L),cadmium acetate+NAC (10mg/L+20mmol/L),group of lead and cadmium(300mg/L+10mg/L),group of lead and cadmium+NAC(300mg/L+10mg/L+20mmol/L),which are given by drinking water during gestational periods.After delivery,neonatal SD rats are used to examine the toxic effects of lead or/and cadmium and appraise protective effect of NAC.Experimental examination index was that①Toxic effect of lead and/or cadmium on physical growth (such as body weight,brain weight) and development of brain;②The studies on the changes in histopathology and ultrastructure of cerebral cortex of the neonatal SD rats;③Toxic effects of lead or/and cadmium on the biochemistry index of neonatal rats brain, such as the activity of GSH-Px,SOD,CAT and TChE and the content of MDA;④Effect of lead or/and cadmium on contents of trace element(Cu,Fe,Zn,Mn and Se) in neonatal rats;⑤The expression of bcl-2,Bax,c-fos in the cerebral cortex by FQ-PCR and MT-3 by FQ-PCR and immunohistochemistry method;⑥The protective effects of NAC on damage of lead or/and cadmium in developing brain of neonatal rats.The results are as follows:①In comparison with the control group,the body weight and brain weight are obviously decreased in lead or/and cadmium group(P＜0.05 or P＞0.05), especially in the combination group;②The changes in histopathology of cerebral cortex is not observed under light microscope.However,the changes in ultrastructure of cerebral cortex is obvious that pyknosis of neuron nucleus,chromatin assemble,mitochondrial swelling and partial cristae under transmission electronic microscope;③In each of experimental groups,the activities of GSH-Px,SOD,CAT and TChE are significantly decreased than those in the normal group(P＜0.05),however,the content of MDA is significantly increased in the experimental group than that in the normal group(P＜0.05);④In the poisoning groups,the contents of trace element(Cu、Fe、Zn、Mn and Se) descend more significantly than the normal group(P＜0.05);⑤In comparison with control group,the expression of bcl-2 in the cerebral cortex decrease(P＜0.05 or P＞0.05),but the expression of Bax,c-fos and MT-3 increase in the experimental groups(P＜0.05 or P＞0.05);⑥In comparison with the poisoning groups respectively,the protective groups of NAC are not only contents of trace element(Cu,Fe,Zn,Mn and Se) are improved,but also the activity of GSH-Px,SOD,CAT and TChE are higher(P＞0.05)and the content of MDA is significantly lower(P＜0.05).The expression levels of bcl-2 in the cerebral cortex is obviously increased(P＜0.05 or P＞0.05),but the expression levels of Bax and c-fos are significantly decreased in the experimental group(P＜0.05).The conclusions drawn by analyzing the test results are as following:①The body weight and brain weight of neonatal rats are significantly decreased by lead or/and cadmium exposed to gestational rats;②There are obvious changes in ultrastructure of the cerebral cortex which displayed as cytomembrane disappearance and neuron nucelus concentration,mitochondrial swelling,disruption and total cristae loss;③The reducing activity of antioxidase led to lead or/and cadmium could be related to the decreasing contents of trace element in neonatal rats;④The apoptosis of neurons induced by lead or/and cadmium are in connection with the exceptional expression of bcl-2、Bax and c-fos genes.It is clear that lead and cadmium combined treatment exerts an synergistic effect;⑤NAC,as a new-style antioxidant,could antagonize toxicity of lead or/and cadmium, which improves activity of antioxidase and reducing lipid peroxidation and increasing content of trace element and increasing gene expression of bcl-2 and decreasing gene expression of Bax、c-fos and MT-3,while its protective effect was limited.
引文
[1]何燧源编.环境毒物[M].北京:化学工业出版社,2002,51-56
[2]廖自基.环境中微量重金属元素的污染危害与迁移转化[M].北京:科学出版社,1989,69-97
[3]杨志新,刘树庆.Cd、Zn、Pb单因素及复合污染对土壤酶活性的影响[J].土壤与环境,2000,9(1):15-18
[4]和文祥.土壤酶与重金属关系的研究现状[J].土壤与环境,2000,9(2):139-142
[5]赵春燕,孙军德,宁伟,等.重金属对土壤微生物酶活性的影响[J].土壤通报,2001,32(2):92-94
[6]史长青.重金属污染对水稻土酶活性的影响[J].土壤通报,1995,26(1):34-35
[7]Kandeler E,Lufienegger G,Schwarz S.Influence of heavy metals on the functional diversity of soil microbialcommunities[J].Bilogy and Fertility of Soils,1997,23:299-306
[8]Khan K S,Xie Z M,Huang C Y.Effects of cadmium,lead and zinc on size of m icrobial biomassin red soil[J].Pedo sphere,1998A,8:27-32
[9]张铣,薛彬,魏雪涛,等.镉免疫毒性机理的初步探讨[J].中国环境科学,1999,19(6):530-535
[10]Mukherji S,Maitra P.Toxic effects of lead on growth and metabolism of germinating rice(Oryza salivaL) seedsand mitosis of onion(Allium cepa L)[J].Indian J Exp Biol,1976,14:519-521
[11]秦天才,吴玉树,王焕校,等.镉、铅及其相互作用对小白菜根系生理生态效应的研究[J].生态学报,1998,18(3):320-325
[12]Jarvis J C,Jones L H P,Hopper M J.Cadmium uptake from solution by plants and its transport from roots to shoots[J].Plant Soil,1976,44:179-191
[13]Cataldo D A,Garland T R,Wildung R E.Cadmium uptake kinetics in intact soybean plants[J].Plant Physiol,1983,73(3):844-848
[14]李玉红,宗良纲,黄耀,等.不同有机酸对水稻吸收铅的影响[J].南京农业大学学报,2002,25(3):45-48
[15]孙铁珩主编.污染生态学[M].北京:科学出版社,2001,160-198
[16]王银秋,张迎梅,赵东芹,等.重金属镉、铅、锌对鲫鱼和泥鳅的毒性[J].甘肃科学学报,2003,15(1):35-38
[17]胡家会,张永忠,张培玉,等.铅、铬和硒对玫瑰无须鱼巴毒性的初步研究[J].经济动物学 报,2004,8(3):171-174
[18]陈亮,郭红岩,沈红,等.低浓度铅暴露对鲫鱼肝脏抗氧化系统的影响[J].环境化学,2002,21(5):485-489
[19]Saint Denis M,Labrot F.Olutathione,Olutathione-Related Enzymes and Catalase Activities in the Earth-worm Eisenia fetida andmi[J].Arch Environ Contam Toxicol,1998,35:602-614
[20]刘艳平,李炼,李忠魁,等.底泥重金属铅对鲤鱼红细胞遗传物质的损伤[J].实用预防医学,2003,10(3):333-335
[21]陈怀满主编.土壤-植物系统中的重金属污染[M].北京:科学出版社,1996,210-252
[22]刘宗平主编.动物中毒病学[M].北京:中国农业出版社,2006,394
[23]阮素云,顾祖维,杨勇骥.采用能谱法研究铅对大鼠血脑屏障的通透性[J].中华预防医学杂志,1999,33(2):107-109
[24]赵正言,邵杰,竺智伟.铅的神经毒理机制研究进展[J].中国实用儿科杂志,2006,21(3):163-165
[25]Adhikari N,Sinha N,Narayan R,et al.Lead-induced cell death in tests of young rats[J].J Appl Toxicol,2001,21(4):275-277
[26]李国君,吴德生,李鹏高,等.醋酸铅引起神经细胞的凋亡[J].卫生毒理学杂志,2001,15(3):156-158
[27]李茂进.铅影响学习记忆的研究进展[J].国外医学卫生学分册,2000,27(3):139-143
[28]Kern M,Audesirk G.In organic lead may inhibit neuritis development in cultured rat hippocampal neurons through hyper phosphorlation[J].Toxicol Appl Pharmacol,1995,134(1):111-123
[29]Costa L G,Fox D A.A selective decrease of cholinergic muscarinic receptors in the visual cortex of adult rats following developmental lead exposure[J].Brain Res,1983,276:259-266
[30]Kishi R,Uchino E.Effects of low lead exposure on neuro-behavioral function in the rat[J].Arch Environ Health,1983,38:25-33
[31]Sharifi A M,Shadi B,Masoomeh J,et al.Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo[J].Neuroscience Letters,2002,329:45-48
[32]Rajat Sandhir,Deepinder Julka,Kiran Dip,et al.Lipoperoxidative damage on lead exposure in rat brain and its implication on membrance bound enzymes[J].Toxicol Appl Pharmacol,1994,74:66-71
[33]Adonaylo V N,Oteiza P I.Lead intoxidation:antidant defense and oxidative damage in rat brain [J].Toxicology,1999,135:77-85
[34]丁训诚,刘春芳,董竞武,等.铅对发育中的脑脂质过氧化作用的影响[J].中国药理学与毒理学杂志,1988,2:293-295
[35]Bouton C M,Frelin L P,Forde C E,et al.Synap totagmin I is a molecular target for lead[J].J Neurochem,2001,76:1724-1735
[36]李权武,王建华.动物繁殖毒理学[M].西安:陕西科学技术出版社,1999
[37]孙素玲,于小丹.醋酸铅对小鼠精子形态影响[J].安徽技术师范学院学报,2001,15(4):383-389
[38]周艳,金丹东,袁小倩.铅对小鼠精子形态影响的观察[J].生物通报,2003,38(3):54-55
[39]马保华,史志诚,艾小云,等.醋酸铅对小鼠受精能力及受精卵发育毒性研究[J].西北大学学报(自然科学版),2006,36(1):93-95
[40]J P Bonde,Mjoffe,P Apostoli,et al.Sperm count and chromatin structure in men exposed to inorganic lead:lowest adverse effect levels Occup[J].Environ Med,2002,59:234-242
[41]Susan Benoff,Grace M Centola,Colleen Millan,et al.Increased seminal plasma lead levels adversely affect the fertility prtential of sperm in IVF[J].Hum Reprod,2003,18:374-383
[42]Tohru Kimura,Akira Suzuki,Yukiko Fujita,et al.Conditional loss or PTEN leads to testicular teratoma and enhances embryonic germ cell production[J].Development,2003,130:1691-1700
[43]Suzanne Jackowski,Jerold E Rehg,Yong-Mei Zhang,et al.Disruption of CCTB2 expression leads to gonadal dysfunction[J].Mol Cell Biol,2004,24:4720-4733
[44]Tian L,Lawrence D A.Lead inhibits nitric oxide production in vitro by murine splenic macrophages[J].Toxicol Appl Pharmacol,1995,132:156-163
[45]Fischbein A,Tsang P,Luo J C,et al.Phenotypic aberrations of CD+3 and CD+4 cell and functional impairments of lymphocytes at low-lead occupational exposure to lead[J].Clin Immunol Immunopathol,1996,66:163-168
[46]Heo Y,Parspns P J,Laurence D A.Lead differentially modifies cytokine production in vitro and in vivo[J].Toxicol Appl Pharmacol,1996,138:149-157
[47]Shen X L,Lee K,Konig R.Effects of heavy metal ions on resting and antigen-activated CD~(4+) T cells[J].Toxicology,2001,169:67-80
[48]Krocova Z,M acela A,Kroca M,et al.The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro[J].Toxicol in Vitro,2000,14:33-40
[49]McCabe M J,Singh K P,Reiners J J.Low level lead exposure in vitro stimulates the proliferation and expansion of alloantigen reactive CD~(4+) high T cells[J].Toxicol Appl Pharmacol,2001,177:219-231
[50]Gupta P,Husain M M,Shankar R,et al.Lead exposure enhances virus multiplication and pathogenes is in mice[J].Vet Hum Toxicol,2002,44:205-210
[51]Bishayi B,Sengupta M.Intracellular survival of staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature swiss albino mice[J].Toxicology,2003,184:31-39
[52]李金有.铅致大鼠心肌细胞巯基水平改变与硒对其影响的研究[J].卫生毒理学杂志,1998,12(3):161-162
[53]朱宝立.金属元素对人胚肺细胞联合毒性的研究[J].江苏预防医学,1996(2):3-5
[54]牛静萍.利用大鼠游离肝细胞的生化指标研究金属化合物的联合毒性[J].中国公共卫生学报,1995,14(2):97-99
[55]蔡虹,翁坤荣.矮小身材儿童头发中8种微量元素分析[J].广东微量元素科学,2004,11(1):32-35
[56]刘希兰,陈陵.微量元素与胚胎生长发育[J].微量元素与健康研究,2003,20(3):52-54
[57]薛会灵,秦英,王树松.围产期铅暴露对胎儿神经系统的影响[J].国外医学妇幼保健分册,2005,16(4):206-207
[58]李晓婷.低水平铅暴露对中枢神经系统的毒性作用及其分子机制[J].今日化学,2005,1:55-64
[59]Markovac J,Goldstein G W.Picomolar concentrations of lead stimulate brain protein kinase C[J].Nature,1988,334:712
[60]Peng S,Hajela R K,Atchison W D.Characteristics of block by Pb~(2+) of function of human neuronal L-,N-,and R-type Ca~(2+) channels transiently expressed in human embryonic kidney 293cells[J].Mol Pharmacol,2002,62(6):1418-1430
[61]Perrier J F,Alaburda A,Hounsgaard J.Spinal plasticity mediated by postsynaptic L-type Ca~(2+)channels[J].Brain Res Brain Res Rev,2002,40(123):223-229
[62]Richardt G,Federolf G,Habermann E.Affinity of heavy metal ions to intracellular Ca~(2+)-binding proteins[J].Biochem Pharmacol,1986,35:1331
[63]Habermann E,Crowell K,Janicki P.Lead and other metals can substitute for Ca~(2+) in calmodulin [J].Arch Toxicol,1983,54:61
[64]Cheung W Y.Calmodulin:Its potential role in cell proliferation and metal toxicity[J].Fed proc,1984,43:2995
[65]孙黎光,邢伟,刘素媛,等.铅对大鼠脑海马神经细胞Ca~(2+)浓度及蛋白激酶C活性的影响[J].卫生毒理学杂志,1997,37:180
[66]Toscano C D,Hashemzadeh Gargari H,McGlothan J L,et al.Developmental Pb~(2+) exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain[J].Brain Res Dev Brain Res,2002,139:217-226
[67]Kandel E R.The molecular biology of memory storage:a dialogue between genes and synapses[J].Science,2001,294:1030-1038
[68]Nihei M K,Desmond N L,McGlothan J L,et al.N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning[J].Neuroscience,2000,99:233-242
[69]Guilarte T R,McGlothan J L.Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb~(2+)-exposed rats:implications for synaptic targeting and cell surface expression of NMDAR complexes[J].Brain Res Mol Brain Res,2003,113(122):37-43
[70]Zhang X Y,Liu A P,Ruan D Y,et al.Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNAs in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry[J].Neurotoxicol Teratol,2002,24(2):149-160
[71]Reddy G R,Basha M R,Devi C B,et al.Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat[J].Int J Dev Neurosci,2003,21(6):347-352
[72]董桂娟,赵正言,竺智伟.铅暴露对生长发育期大鼠不同脑区一氧化氮合酶活力的影响[J].中华劳动卫生职业病杂志,2003,21(4):263-265
[73]Zhu Z W,Yang R L,Dong G J,et al.Study on the neurotoxic effects of low-level lead exposure in rats[J].J Zhejiang Univ Sci,2005,6(7):686-692
[74]余绍蕾,蔡宇.枸杞多糖对染铅小鼠海马区NO和NOS活性的影响[J].中药药理与临床,2006,22(1):41-42
[75]Chetty C S,Reddy G R,Murthy K S,et al.Perinatal lead exposure alters the expression of neuronal nitric oxide synthase in rat brain[J].Int J Toxicol,2001,20(3):113-120
[76]王韵,韩济生.一氧化氮在医学中的现在和将米[J].生理科学进展,1999,30(1):94-95
[77]王静,李积胜,张进,等.铅对小鼠海马一氧化氮合酶活力及表达的影响[J].中华劳动卫生职业病杂志,2000,18(4):204-206
[78]Savolainen K M,Loikkanen J,Eerikainen S,et al.Interactions of excitatory neurotransmitters and xenobiotics in excitotoxicity and oxidative stress:glutamate and lead[J].Toxicol Lett,1998,102:363
[79]牛玉杰,张荣,程云会,等.醋酸铅对小鼠脑细胞凋亡及Bcl-2、bax基因表达的影响[J].中华预防医学杂志,2002,36(1):30-33
[80]文涛,孙黎光,彭博.慢性铅暴露小鼠脑海马c-fos、c-jun表达与学习记忆的关系[J].毒理学杂志,2005,19(3):236
[81]蔡宇,余绍蕾,张荣华.枸杞多糖对染铅小鼠行为功能保护及脑细胞Fas抗原表达的影响[J].环境与职业医学,2005,22(6):533-534
[82]Stohs S J,Bagchi D.Oxidative mechanisms in the toxicity of metal ions[J].Free Radic Biol Med,1995,18:321-336
[83]陆新华,刘卓宝.自由基与铅中毒机制的研究进展[J].中华劳动卫生职业病杂志,1998,16(3):189-191
[84]陆巍.铅的神经毒作用机制[J].国外医学卫生学分册,1995,22:341-343
[85]王桂芝,刘双年,候玉春,等.铅对大鼠脑细胞脂质过氧化及超氧物歧化酶活性的影响[J].卫生毒理学杂志,1995,9:175
[86]Winder C,Bonin T.The genotoxicity of lead[J].Mutation Res,1993,285(1):117-124
[87]Hartwig A.Interactions by carcinogenic metal compounds with DNA repair processes:toxicological implications[J].Toxicol Lett,2002,127(1-3):47-54
[88]Restrepo H G,Sicard D,Torres M M.DNA damage and repair in cells of lead exposed people[J].Am J Ind Med,2000,38(3):330-334
[89]Razmiafshari M,Kao J,d'Avignon A,et al.NMR identification of heavy metal-binding sites in a synthetic zinc finger peptide:toxicological implications for the interactions of xenobiotic metals with zinc finger proteins[J].Toxicol Appl Pharmacol,2001,172(1):1-10
[90]Quintanilla-Vega B,Hoover D J,Bal W,et al.Lead interaction with human protamine(HP2) as a mechanism of male reproductive toxicity[J].Chem Res Toxicol,2000,13(7):594-600
[91]Rydberg B.Radiation-induced DNA damage and chromatin structure[J].Acta Oncol,2001,40(6):682-685.
[92]GB16297-1996,中华人民共和国国家标准大气污染物综合排放标准[S].北京:国家环境保护局,1996
[93]GB 3838-2002,中华人民共和国地表水环境质量标准[S].北京:中国环境科学出版社出版,2002
[94]天津大学图书馆.环境科学与工程学科信息数据库[DB/OL]http://202.113.6.254/hi/web,2003-3-25
[95]赵璇,吴天宝.我国饮用水源的重金属污染及治理技术深化问题[J]_给水排水,1998,24(10):22-25
[96]邹国良.保护土壤环境是我们的历史责任[J].中国科学报,1989年1月10日第1版
[97]周锡爵.张士灌区镉污染及其解决和利用的途径[J].农业环境保护,1987,6(2):17-19
[98]刘立群.赣南土壤污染的防治途径[J].资源开发与保护杂志,1990,6(2):100-102
[99]王江平.入世后高浓度磷肥中镉的问题[J].磷肥与复肥,2002,17(5):11-15
[100]Research Triangle Institute.Toxicological profile for cadmium[R].Prepared for U.S.Agency for Toxic Substances and Disease Registry,July 1999
[101]王夔主编.生命科学中的微量元素(第二版)[M].北京:中国计量出版社,1996,7:850-882
[102]江中良,王立强,李青旺,等.镉对哺乳动物繁殖性能的影响[J].四川畜牧兽医,2002,29(1):29
[103]Kotsonis F N,Klaassen C D.Toxicity and distribution of cadmium administration to rats at sublethal doses[J].Toxicol Appl Pharmacol,1977,46(1):39-54
[104]Kotsonis F N,Klaassen C D.The relationship of metallothionein to the toxicity of cadmium after prolonged oral administration to rats[J].Toxicol Appl Pharmacol,1978,46(1):39-54
[105]Sato K,Iwamasa T,Tsuru T,et al.An ultrastructural study of chronic cadmium chloride-induced neuropathy[J].Acta Neuropathol(Berl),1978,41(3):185-190
[106]Murthy R C,Saxena D K,Lal B,et al.Chronic cadmium-ethanol administration alters metal distribution and some biochemicals in rat brain[J].Biochem Int,1989,19(1):135-143
[107]Valois A A,Webster W S.The choriod plexus as a target site for cadmium toxicity following chronic exposure in the adult mouse:An ultrastructural study[J].Toxicology,1989,55:193-205
[108]刘伟成,李明云.镉毒性毒理学研究进展[J].广东微量元素科学,2005,12(12):1-5
[109]刘利娟,丁雄,唐玲,等.锌、镉与儿童中枢神经系统疾病51例分析[J].微量元素与健康研究,1994,11(4):59
[110]马军,斯欣,叶广俊.环境镉污染对儿童学习记忆的影响[J].中国学校卫生,2000,21(6):440-441
[111]戈果,王景传,许庭良,等.V_E对慢性镉中毒小鼠黑质神经元的保护作用[J].中国地方病学杂志,2002,21(6):450-452
[112]李湘鸣,居中华,孙蓉,等.镉对大鼠睾丸中某些酶活性及组织形态的影响[J].卫生毒理学杂志,1999,13(1):31-33
[113]李建秀,王晓梅.氯化镉对小鼠精子的影响[J].工业卫生与职业病,1997,23(4):213-214
[114]Saygi S,Deniz G,Kutsal O,et al.Chronic effects of cadmium on kidney,liver,testis,and fertility of male rats[J].Biol Trace Elem Res,1991,31(3):209-214
[115]Mohan J,Moudgal R P,Panda J N.Effects of cadmium salt on phosphomonoesterases activity and fertilizing ability of fowl spermatozoa[J].Indian J Exp Biol,1992,30(3):241-243
[116]杨建明,陈琼宇,曾祥斌,等.镉对雄性生育功能的影响[J].中国公共卫生,2000,1(4):313-314
[117]Machemer L,Lorke D.Embryotoxic effect of cadmium on rats upon oral administration[J].Toxicol Appl Pharmacol,1981,58:438-443
[118]Levin A A,Miller R K.Fetal toxicity of cadmium in the rat:decreased utero-placental blood flow [J].Toxicol Appl Pharmacol,1981,58(2):297-306
[119]庞惠民,朱玉琢,刘念稚.益母草对硫酸镉诱发的小鼠骨髓细胞微核率的影响[J].吉林大学学报(医学版),2002,28(5):463-464
[120]Lafuente A,Blanco A,Marquez N,et al.Effects of acute and subchronic cadmium administration on pituitary hormone secretion in rat.[J].Rev Esp Fisiol,1997,53(3):265-269
[121]Esquifino A I,Marquez N,Alvarez Demanuel E,et al.Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats[J].J Trace Elements Med Biol,1999,12(4):205-210
[122]曾祥斌,金泰,周袁芬,等.镉对大鼠血清性激素水平的影响[J].中华劳动卫生职业病杂志,2001,19(6):430-432
[123]张文昌,吴志仁,李煌元,等.染镉雌性大鼠垂体、卵巢对性腺激素的反应机能状况[J].卫生毒理学杂志,2002,16(1):24-26
[124]Blakley B R.Humoral immunity in aged mice exposed to cadmium[J].Can J Vet Res,1988,52(2):291-292
[125] Exon J H, Koller L D, Kerkvliet N I. Tissue residues, pathology and viral-induced mortality in mice chronically exposed to different cadmium salts [J]. J Environ Pathol Toxicol Oncol, 1986, 7(1-2): 109-114
[126] Blakley B R. The effect of cadmium chloride on the immune response in mice [J]. Can J Comp Med, 1985,49(1): 104-108
[127] Blakley B R. The effect of cadmium on chemical- and viral-induced tumor production in mice [J]. J Appl Toxicol, 1986, 6(6): 425-429
[128] Chopra R K, Prasad R, Sharma N, et al. Effect of dietary chronic cadmium exposure on cell-mediated immune response in Rhesus monkeys (Macaca mulatta): Role of calcium deficiency [J]. Arch Toxicol, 1984, 56(2): 128-131
[129] Stacey N H, Craig G, Muller L. Effects of cadmium on natural killer and killer cell functions in vivo [J]. Environ Res, 1988, 45(1): 71-77
[130] Daniels M J, Menache M G, Burleson G R,et al. Effects of NiCl_2 and CdCl_2 on susceptibility to murine cytomegalovirus and virus-augmented natural killer cell and interferon responses [J]. Fundam Appl Toxicol, 1987, 8(4): 443-453
[131] Stacey N H. Effects of cadmium and zinc on spontaneous and antibody-dependent cell- mediated cytotoxicity [J]. J Toxicol Environ Health, 1986, 18(2): 293-300
[132] Prigge E. Early signs of oral and inhalative cadmium uptake in rats [J]. Arch Toxicol, 1978, 40(3): 231-247
[133] Groten J P, Sinkeldam E L, Luten J B, et al. Comparison of the toxicity of inorganic and liver-incorporated cadmium: A 4-week feeding study in rats [J]. Food Chem Toxicol, 1990,28(6): 435-441
[134] Masaoka T, Akahori F, Arai S, et al. A nine-year chronic toxicity study of cadmium ingestion in monkeys. I. Effects of dietary cadmium on the general health of monkeys [J]. Vet Hum Toxicol, 1994,36(3): 189-194
[135] Hays E S, Marga retten N. Long-term oral cadmium produces bone marrow hypoplasia in mice [J]. Exp Hematol, 1985, 13(3): 229-234
[136] Sakata S, Iwami K, Enoki Y, et al. Effects of cadmium on in vitro and in vivo erythropoiesis: Erythroid progenitor cells (CFU-E) iron, and erythropoietin in cadmium-induced iron deficiency anemia [J]. Exp Hematol, 1988, 16(7): 581-587
[137]Wilson R H,DeEds F,Cox A J.Effects of continued cadmium feeding[J].J Pharmacol Exp Therap,1941,71:222-235
[138]Schroeder H A.Cadmium as a factor in hypertension[J].J Chronic Dis,1965,18:647-656
[139]Jamall I S,Naik M,Sprowls J J,et al.A comparison of the effects of dietary cadmium on heart and kidney oxidant enzymes:Evidence for the greater vulnerability of the heart to cadmium toxicity[J].JAppl Toxicol,1989,9:339-345
[140]王强,姚素梅,郭秀珍.急性镉中毒大鼠致死时重要器官的镉分布[J].广东微量元素科学,1998,5(9):23-26
[141]Shigematsu I.The epidemiological approach to cadmium pollution in Japan[J].Ann Acad Med Singapore,1984,13:231-236
[142]Nogawa K,Tsuritani I,Kido T,et al.Serum vitamin D metabolites in cadmium-exposed persons with renal damage[J].Int Arch Occup Environ Health,1990,62:189-193
[143]Buchet J P,Lauwerys R,Roels H,et al.Renal effects of cadmium body burden of the general population[J].Lancet,1990,336:699-702
[144]刘杰.镉的毒性和毒理学研究进展[J].中华劳动卫生职业病杂志,1999,16(1):2-4
[145]Carageorgiou H,Tzotzes V,Pantos C,et al.In vivo and in vitro effects of cadmiumon adult rat brain total antioxidant status,acetylcholinesterase,(Na~+,K~+) ATPase and Mg~(2+)ATPase activities:protection by L-cysteine[J].Basic Clin Pharmacol Toxicol,2004,94(3):112-118
[146]Faurakov B,Bjerregaard H F.Evidence for cadmium mobilization of intra cellular calcium through a divalent cation receptor in renal distal epithelial A6 cells[J].Pflugers Arch,2002,445(1):40-50
[147]Gadbut A P,Cash S A,Noble J A,et al.The effect of Ca~(2+) channel antagonists(Cadmium,omega-conotoxin GIVA,and nitrendipine) on the release of angiotensin Ⅱ from fetal rat brain in vitro[J].Neurosci Lett,1991,123(1):91-94
[148]Dudel J,Pamas H,Parnas I.Evoked phasic release in frog nerve terminals obtained after block of Ca~(2+) entry by Cd~(2+)[J].Pflugers Arch,1991,419(2):197-204
[149]Smith J B,Dwyer S D,Smith L,et al.Cadmium evokes ino sitol polyphosphate formation and calcium mobilization[J].J Biol Chem,1989,264:7115
[150]马军,斯欣,叶广俊.镉对神经细胞内游离钙浓度的影响[J].中国公共卫生学报,1996,15(1):21-23
[151]Blazka M E,Shaikh Z A.Difference in cadmium and mercury uptakes by hepatocytes:Role of calcium channels[J].Toxicol Appl Pharmacol,1991,110:355-363
[152]Yang C F,Shen H M,Shen Y,et al.Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts(MRC-5cells)[J].Environ Health Perspect,1997,105:712-716
[153]Muller L.Consequences of cadmium toxicity in rat hepatocytes mitochondrial dysfunction and lipid peroxidation[J].Toxicology,1991,40:285
[154]Bagchi D,Vuchetich P J,Bagchi M.Induction of oxidative stress by chronic administration of sodiumdi-chromate[chromium Ⅵ]and cadmium chloride[cadmium]to rats[J].Free Radic Biol Med,1997,22(3):471-478
[155]Karmakar R,Roy S,Chatterjee M.The effects of cadmium on the hepatic and renal levels of reduced glutathione,the activity of glutathione S-transferase and gamma glutamyl transpeptidase [J].J Environ Pathol Toxicol Oncol,1999,18(1):29-35
[156]Shukla A,Shukla G S,Srimal R C.Cadmium-induced alterations in blood-brain barrier permeability and its possible correlation with decreased micro vessel antioxidant potential in rat [J].Hum ExpToxicol,1996,15(5):400-405
[157]Briehl M M,Baker A F.Modulation of the antioxidant defense as a factor in apoptosis[J].Cell Death Different,1996,3:63-70
[158]Hart B A,Enema J D,Potts R J,et al.Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells and its potential involvement in cadmium carcinogenesis[J].Toxicology,2000,147:215-228
[159]余日安,陈学敏.镉对大鼠肝细胞原癌基因c-fos、c-jun表达的影响[J].卫生研究,2000,29(6):364-365
[160]余日安,陈学敏.镉对大鼠肝细胞原癌基因c-myc表达的影响[J].中国公共卫生,2000,16(11):995-996
[161]Margoshes M,Vallee B L.A cadmium protein from equine kidney cortex[J].J Amer Chem Soc,1957,(79):4813
[162]Quafe C J,Findley S D,Ericksin J C,et al.Induction of new metallothione in isoform(MT-2)occurs during differentiation of stratified squamous epithelia[J].Biochemistry,1994,33:7250-7259
[163]McKenna I M,Bare R M,Waalkes M R Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium[J].Toxicology,1996,107(2):121-130
[164]任宏伟,茹炳根.金属硫蛋白(Metallothionein,MT)基因在转基因领域的应用[J].生物工程进展,2000,20(4):35-39
[165]张博润,蔡向荣,怀文辉,等.金属硫蛋白的研究进展及应用前景[J].微生物学报,1999,26(5):355-357
[166]Cherian M G,Goyer R A.Metallothioneins and their role in the metabolism and toxicity of metals[J].Life Sci,1978,23(1):1-9
[167]Emily F M,Brunce A F.Mechanisms of nephrotoxicity from metal combinations:a review[J].Drug Chem Toxicol,2000,23(1):1-12
[168]Karpela A,Louenira R,Yrjanheikki E,et al.Lead and cadmium concentrations in maternal and umbilical cord blood,amniotic fluid,placenta,an amniotic membranes[J].Ann J Obstet Gynecol,1986,155,1086-1089
[169]Antonio M T,Corpas I.,Leret M L.Neurochemical changes in newborn rat's brain after gestational cadmium and lead exposure[J].Toxicol Lett,1999,104,1-9
[170]刘艳虹.铅对儿童神经系统毒性作用的研究进展[J].中国特殊教育,2006,67(1):62-65
[171]A Pillai L,Priya S Gupta.Effects of combined exposure to lead and cadmium on the hypothalamic-pituitary axis function in proestrous rats[J].Food Chem Toxicol,2003,41:379-384
[172]Lynch G P,Smith D F,Fisher M,et al.Physiological responses of calves to cadmium and lead[J].J Anita Sci,1976,42,410-421
[173]Burrows,G.E.,Borchard,R.E.Experimental lead toxicosis in ponies:Comparison of the effects of smeiler effluents,contaminated hay and lead acetate[J].Am J Vet Res,1982,43,2129-2133
[174]Mihaud G E,Mehennaoui S.Indicaters of lead,Zinc and cadmium in cattle.I.Results in a polluted area[J].Vet Hum Toxicol,1988,30(6):513-517
[175]Cibulka J,Miholova D,Pi sa J,et al.Natural levels of lead,cadmium and mercury in tissues and hair of newborn calves from different areas of czechoslovakia[J].Sci total environ,1989,84:101-112
[176]刘宗平,马卓,李文范,等.铅镉中毒发病机理的研究-绵羊动物模型的复制[J].中国兽医科技,1996,26(10):11-14
[177]王学谦,尹先仁,白雪涛.铅镉联合作用对大鼠肾小管上皮细胞脂质过氧化的影响[J].卫 生研究,2002,31(4):232-234
[178]Patricia Bizarro,Sandra Acevedo,Geraldine Nino-Cabrera,et al.Ultrastructural modifications in the mitochondrion of mouse Sertoli cells after inhalation of lead,cadmium or lead-cadmium mixture[J].Reprod Toxicol,2003,17,561-566
[179]王兰,杨秀清,王茜,等.镉在河蟹五种组织器官的积累及对酯酶同工酶的影响[J].动物学报,2001,47(专刊):96-100
[180]陈卫平,刘世杰.铅的肾细胞毒性及锌的保护作用[J].卫生毒理学杂志,1995,9(2):73-76
[181]马卓,刘宗平,张白银,等.绵羊铅镉联合中毒与硒解毒的试验病理学研究[J].中国兽医科技,1997,27(3):12-14
[182]Liu Z P.Lead poisoning combined with cadmium in sheep and horses in the vicinity of non-ferrous metal smelters[J],The Science of the Total Environment,2003,309:117-126
[183]Nation J R,Frye G D,VonStultz J,et al.Effects of combined lead and cadmium exposure:changes in schedule-controlled responding and in dopamine,serotonin and their metabolites[J].Behav Neurosci,1989,103(5):1108-1114
[184]Nation J R,Grover C A,Bratton G R,Salinas J A.Behavioural antagonism between lead and cadmium[J].Neurotoxicol Teratol,1990,12:99-104
[185]Mahaffey K R,Caper S G,Gladen B C,et al.Concurrent exposure to lead,cadmium and arsenic [J].J Lab Clin Med,1981,98:463-480
[186]Haneef S S,Swarup D,Dwivedi S K,et al.Effects of concurrent exposure to lead and cadmium on renal function in goats[J].Small Rumin Res,1998,28,257-261
[187]Nolan C V,Shaikh Z A.Lead nephrotoxicity and associated disorders:Biochemical mechanism [J].Toxicol,1992,73:127-146
[188]Anilkumar Pillail,Sarita Gupta.Effect of gestational and lactational exposure to lead and/or cadmium on reproductive performance and hepatic oestradiol metabolizing enzymes[J].Toxicol Lett,2005,155:179-186
[189]金建年,彭文娟,彭兆麟.痰净雾化液超声雾化吸入祛痰作用研究[J].湖北中医杂志,1999,21(4):157
[190]李长生,杨炯,李清泉,等.乙酰半胱氨酸胶囊止咳祛痰作用的临床研究[J].中国医院药学杂志,1999,19(11):676
[191]Gregory S,Kelly N D.Clinical Applications of N-acetylcysteine[J].Altern Med Rev,1998,3: 114
[192]代心平.N-乙酰半胱氨酸药理与保健作用研究[J].海南医学,2004,12(10):121-122
[193]Lailey A F.Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats[J].Hum ExpToxicol,1997,16:212-216
[194]王雨,徐兆发,喻道军,等.N-乙酰半胱氨酸和亚硒酸钠对镉亚慢性毒性的影响[J].毒理学杂志,2005,19(4):251-253
[195]Ueland P M,Mansoor M A,Guttormsen A B,et al.Reduced oxidized and protein-bound forms of homocysteine and other aminothiol in plasma comprise the redox thiol status—a possible element of the extracelluar antioxidant defense system[J].J Nutr,1996,126(4Suppl):1281
[196]Labib R,Abdel-Rahman M,Turkall R.N-acetvlcvsteine pretreatment decreases cocaine and endotoxin-induced hepatotoxicity[J].J toxicol environ health,2003,66(3):223-239
[197]Buhimschi L A,Buhimschi C S,Weiner C P.Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation[J].Am J obstet gynecol,2003,188(1):203-208
[198]Allegra L,Dal Sasso M,Bovio C,et al.Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations[J].Arzneimittelforschung,2002,52(9):669-676
[199]Dick C A,Brown D M,Donaldson K.The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types[J].Inhat Toxicol,2003,15(1):39-52
[200]Cammer W.Protection of cultured oligodendrocytes against tumor necrosis factor-alpha by the antioxidants coenzyme Q(10) and N-acetylcysteine[J].Brain Res Bull,2002,58(6):587-592
[201]Malins D C,Hellstrom K E,Anderson K M.Antioxidant-induced changes in oxidized DNA[J].Proc Natl Acad Sci USA,2002,99(9):5937-5941
[202]Recchioni R,Marcheselli F,Moroni F,et al.Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by N-acetyl-L-cysteine[J].Metabolism,2002,51(11):1384-1388
[203]De Flora S,Izzotti A,D'Agostini F,et al.Mechanism of N-acetylcysteine in the prevention of DNA damage and cancer,with special reference to smoking-related end-points[J].Carcinogenesis,2001,22(7):999
[204]Srianujata S.Lead-the toxic metal to stay with human[J].J Toxicol Sci,1998,23(2):237-240
[205]童建,冯致英.环境化学物的联合毒性作用[M].上海:上海科学技术文献出版社,1994,1
[206]洪庆涛,唐一鹏.新生大鼠大脑皮层神经细胞的体外原代培养[J].神经解剖学杂志,1994,10(3):259-261
[207]Davis G E,Manthorpe M,Williams L R,et al.Characterization of a laminin-containing neurite-promoting factor and a neuronotrophic factor from peripheral nerve and related sources [J].Ann N Y Acad Sci,1986,486:194-205
[208]Scortegagna M,Hanbauer I.The effect of lead exposure and serum deprivation on mesencephalic primary cultures[J].Neurotoxicology,1997,18(2):331-340
[209]Nakai J.Dissociated dorsal root ganglia in tissue culture[J].Am J Anat,1956,99:81-129
[210]Koh J Y,Choi D W.Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay[J].J Neurosci Methods,1987,20:83-90
[211]Mandell J W,Banker G A.Selective blockade of axonogenesis in cultured hippocampal neurons by the tyrosine phosphatase inhibitor orthovanadate[J].J Neurobiol,1988,35:17-28
[212]罗湘颖,杨志敏,王廷华.胎鼠大脑皮质神经元的体外培养及鉴定[J].神经解剖学杂志,2004,20(5):505-508
[213]赵林普,肖定华,陈士英.脑神经细胞的培养[J].生理科学,1983,3:8-9
[214]Silva R F M,Falcao A S,Fernandes A,et al.Dissociated primary nerve cell cultures as models for assessment of neurotoxicity[J].Toxicol Lett,2006,163:1-9
[215]Katharine M W,Haberstroh,Carolyn M Kapron.Activation of c-Jun N-terminal kinase by cadmium in mouse embryo neural cells in vitro[J].Environ Toxicol Pharmacol,2006,22:1-7
[216]吴希如.哺乳动物胚胎神经细胞原代分离性单层培养及其应用[J].生理科学进展,1984,15(3):25
[2171 郑肇青,张宇,张策.探讨单细胞记录和神经细胞培养时神经元的分离方法[J].山西医科大学学报.2005,36(4):516-518
[218]鄂征主编.组织培养技术及其在医学研究中的应用[M].北京:中国协和医科大学出版社,2004,65-69
[219]潘永英,彭书岐,赵一凡,等.大鼠海马神经元的原代无血清培养及鉴定[J].实用医学杂志,2006,22(7):758-759
[220]Brewer G J,Torricelli J R,Evege E K,et al.Optimized survival of hippocampal neurons in B27-supplemented neuronbasal,a new serum-free medium combination[J].J Neurosci Res,1993,35(5):567-576
[221]丁爱石,王富庄.新生大鼠海马神经元在无血清培养液中的生长特性[J].细胞生物学杂志,1993,15(2):88-90
[222]McKinney J S,Willoughby K A,Liang S,et al.Stretch-induced injury of cultured neuronal,glial,and endothelial cell.Effect of polyethylene glycol-conjugated superoxide dismutase[J].Stroke,1996,27:934-940
[223]Hayashi K,Kawai-Hirai R,Ishikawa K,et al.Reversal of neuronal polarity characterized by conversion of dendrites into axons in neonatal rat cortical neurons in vitro[J].Neuroscience,2002,110:7-17
[224]宋岳涛,洪庆涛,唐一鹏.阿糖胞苷对原代培养的大鼠大脑皮质神经元的影响[J].解剖学杂志,2004,27(6):696-699
[225]Muller H W,Seifert W.A neurotrophic factor(NTF) released from primary glial cultures supports survival and fiber outgrowth of cultured hippocampal neurons[J].J Neurosci Res,1982,8:195-204
[226]Muller H W,Beckh S,Seifert W.Neurotrophic factor for central neurons[J].Proc Natl Acad Sci USA,1984,81:1284-1292
[227]邵延坤,王溪原,于越晖,等.乳鼠皮质神经元原代培养与观察[J].吉林医学,2003,24(2):103-104
[228]晏雪生,彭亚琴,民安萍.人胚大脑皮层神经元细胞体外培养方法的建立[J].中国自然医学杂志,2002,4(4):225-226
[229]曾可斌,胡长林,陈阳美.大鼠海马神经元培养与鉴定[J].基础医学与临床,2004,24(5):574-577
[230]胡前胜,董胜璋,陈学敏,等.低剂量铅对原代培养的海马神经元的影响[J].中国公共卫生,2003,19(5):518-520
[231]杨烽,李积胜,杨芳.不同浓度醋酸铅对大鼠原代培养大脑皮层神经元的影响[J].中华劳动卫生职业病杂志,2004,22(3):217-218
[232]陈军,祝卫国,陈秋生,等.铅对体外培养大鼠海马神经细胞生长和Oct-2蛋白表达的影响[J].中华预防医学杂志,2004,38(3):151-153
[233]Prozialeck W C,Grunwald G B,Dey P M,et al.Cadherins and NCAM as potential targets in metal toxicity[J].Toxicol Appl Pharmacol,2002,182:255-265
[234]Shabani A,Rabbani A.Lead nitrate induced apoptosis in alveolar Macrophages from rat lung [J].Toxicology,2000,149(2-3):109-114
[235]De la Fuente H,Portales-Perez D,Baranda L,et al.Effects of arsenic,cadmium and lead on the induction of apoptosis of normal human mononuclear cells[J].Clin Exp Immunol,2002,129(1):69-77
[236]程云会,牛玉杰,张荣,等.醋酸铅对大鼠脑细胞凋亡及对Fas抗原表达的影响[J].卫生毒理学杂志,2002,16(4):226-227
[237]Huxtable.R J.Physiological Action of Taurine[J].J Physiol Revi,1992,72(1):101-142
[238]Kelly S A,Havrilla C M,Brady T C,et al.Oxidative stress in toxicology:established mammalian and emerging piscine model systems[J].Environ Health Perspect,1998,106(7):375-384
[239]Findel T,Holbrook N J.Oxidants,oxidative stress and the bilolgy of aging[J],Nature,2000,408:239-247
[240]孙存普,张建中,段绍瑾.自由基生物学导论[M].合肥:中国科学技术大学出版社,1999,150-156
[241]Cobson K B.The interaction of cadmium and certain other metal ions with proteins and nucleic acids[J].Toxicology,1980,16:1-37
[242]蔡原,姜厚波,张颖花,等.铅对大鼠肾脏的脂质过氧化作用[J].中国医科大学学报,1994,23(6):21-23
[243]孔繁翔.环境生物学[M].北京:高教出版社,2000,68
[244]王维娜,王安利,孙儒泳.水环境中的铜锌铁钴离子对日本沼虾消化酶和碱性磷酸酶的影响[J].动物学报,2001,47(专刊):72-77
[245]Sieg D J,Billings R E.Lead/Cytokine-mediated oxidative DNA damage in cultured mouse hepatocytes[J].Toxicol Appl Pharmacol,1997,142:106-115
[246]Sies H.Glutathione disulfide(GSSG) effiux from cells and tissues[J].Methods Enzymol,1984,105:445-451
[247]程元恺.谷胱甘肽的解毒作用与毒物代谢物[J].生物化学与生物物理进展,1994,21(5):395-399
[248]Gillissen A,Scharling B,Jaworska M,et al.Oxidant scavenge function of ambroxol in vitro:a comparison with N-Acety leysteine[J].Res Exp Med,1997,196:389-393
[249]殷宪敏,杨明峰,刘瑞锁.N-乙酰-L-半胱氨酸对缺氧新生大鼠脑保护作用的研究[J].中华儿科杂志,2001,39(9):566
[250]Flora G J S,Seth P K.Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dhydratase,glutathione and lipid peroxidation during acute lead-ethanol administration in mice [J].Alcohol,1999,18:103-108
[251]周宜灿,陈晓春,朱元贵,等.N-乙酰半胱氨酸防止帕金森病鼠黑质神经元凋亡[J].中国神经科学杂志,2003,19(6):384-388
[252]Bradbury M W,Deane R.Permeability of the blood-brain barrier to lead[J].Neurotoxicology,1993,14:131-136
[253]Agodi A,Viola M,Alberghina M,et al.Effect of low dose lead acetate exposure on the metabolism of nucleic acids and hippocampus of rat during postnanal development[J].Neurosci Res,1990,25:131-137
[254]Huseman C A,Moriarty C R,Angle C K.Childhood lead toxicity and impaired release of thyotropin stimulation hormone[J].Environ Res,1987,42(2):524-533
[255]Eck P C,Wilson L.Toxic Metals in Human Health and Disease[M].Eck Institute of Applied Nutrition and Bioenergetics;1989
[256]Roels H A,Hoet P,Lison D.Usefulness of biomarkers of exposure to inorganic mercury,lead,or cadmium in controlling occupational and environmental risks of nephrotoxicity[J].Ren Fail,1999,21(3-4):251-262
[257]Osterloh J D,Selby J V,Bernard B P,et al.Body burdens of lead in hypertensive nephropathy[J].Arch Environ Health,1989,44(5):304-310
[258]李晔.碘·生命·健康[M].北京:科学出版社,1998,2
[259]郭宝林,贾志海,张玉枝.畜禽铜营养研究进展[J].饲料工业,2005,26(10):48-51
[260]颜世铭,熊丽萍.元素间的相互影响[J].广东微量元素科学,2000,7(11):1-6
[261]曹盛丰,杨丽娥.高碘高铁日粮对产蛋母鸡代谢酶活力和蛋营养成分的影响[J].饲料博览,2000,13(6):5
[262]Cao J,Luo X G.Effect of dietary iron on concentration,age,and length of iron feeding on feed intake and tissue iron concentration of broiler chicks for use as bioassay of supplemental iron sources[J].Poult Sci,1996,75:495
[263]王俊改,马军,吴南屏,等.硒与镉对小鼠肝、肾睾丸组织脂质过氧化作用的交互影响[J]. 中国公共卫生学报,1997,16(1):37-38
[264]Cooper,G P,Manalis,R S.Interaction of lead and cadmium on acetylcholine release at the frog neuromuscular junction[J].Toxicol Appl Pharmacol,1984,74,411-416
[265]张卓然主编.培养细胞学与细胞培养技术[M].上海:上海科学技术出版社,2004,310.
[266]Heid C A,Stevens J,Livak J K,et al.Real time quantitative PCR[J].Genome Res,1996,6(10):986-994
[267]Livak K J,Schittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J].Methods,2001,25:402-408
[268]Hiquchi R,Fockler C,Dollinqer G,et al.Kinetic PCR analysis:real-time monitoring of DNA amplification reactions[J].Biotechnology(N Y),1993,11(9):1026-1030
[269]Ke L D,Chen Z,Yung W K.A reliability test of standard-based quantitative PCR:exogenous standards[J].Mol Cell Probes,2000,14(2):127
[270]Becker K D Pan,Whitely C B.Real-time quantitative polymerase chain reaction to assess gene transfer[J].Hum Gene Ther,1999,10:2559
[271]Higgins J A,Ezzell J,Hinnebusch B J,et al.5' nuclease PCR assay to detect Yersinia pestis[J].J Clin Microbiol,1998,36(8):2284-2288
[272]Bustin S A.Absolute quantitation of mRNA using real-time reverse ranscription polymerase chain reaction assays[J].J Mol Endocrinol,2000,25:169-193
[273]Anderson A J,Pike C J,Cotman C W,et al.Differential induction of immediate early gene proteins in cultured neurons by beta-amyloid(A beta):association c-jun with A beta-induced apoptosis[J].Neurochem,1995,65:1487-1498
[274]周伟,吴圣楣,陈惠全.Bcl-2,Bax mRNA在新生大鼠缺血缺氧后的表达及其与脑细胞凋亡的关系[J].新生儿杂志,2001,16(2):69-72
[275]Marina Nedelcheva,Tanya Topouzova,Ginka Genova.Transcription of Dfos is stimulated by brain tumours of l(2)gl-deficient larvae of drosophila melanogaster[J].Int J Biochem Cell Biol,2001,33(1):45-51
[276]程金平,王文华,贾金平.氯化甲基汞对大鼠海马c-jun蛋白表达的影响[J].中国环境科学,2003,23(4):431-434
[277]程金平,王文华,贾金平.氯化甲基汞对大鼠脑c-fos、c-jun基因表达的影响[J].环境科学,2003,24(1):52-56
[278]Stephenson C P,Hunt G E,Topple A N,et al.The distribution of 3,4-methylenedioxymet ha-mphetamine ecstasy induced c-fos expression in rat brain[J].Neuroscience,1999,92(3):1011-1023
[279]Moore J,Boswell S,Hoffman R,et al.Mutant H-ras over-expression inhibits a random apoptotic nuclease in myeloid leukemia cells[J].Leukemia Res,1993,17:703-709
[280]Gonzalez-Martin C,de Diego I,Crespo D,et al.Transient C-fos expression accompanies naturally cell death in the developing interbem ispheric cortex of the rat Brain[J].Res Dev Brain Res,1992,68(1):83-95
[281]Chen S C,Curran T,Morgan J I.Apoptosis in the nervous system:new revelations[J].Clin Pathol,1995,48(1):7-12
[282]Hu L,Hatano M,Ruther U,et al.Overexpression of c-fos induces apoptosis of CD43+ pro-B cells[J].J Immunol,1996,157(9):3804-3811
[283]Dhalla N S,Elmoselhi A B,Hata T,et al.Status of myocardial antioxidants in ischemia-reperfusion injury[J].Cardiovasc Res,2000,47(3):446-459
[284]Inserte J,Taimor G,Hofstaetter B,et al.Influence of simulated ischemia on apoptosis induction by oxidants stress in adult cardiomyocytes of rat[J].Am J Physiol Heart Circ Physiol,2000,278(1):94-99
[285]Uchida Y,Takio K,Titani K et al.The Growth Inhinitory Factor That Is Deficient in the Alzheimer's Disease Brain Is a 68 Amino Acid Metallothionein-like Protein[J].Neuron,1991,7:337-347
[286]Palmiter R D,Findley S D,Whitmore T E,et al.MT-,a brain-specific member of the metallothionein gene family[J].Proc Natl Acad Sci USA,1992,89:6333-6337
[287]Liu W,Saint D A.A new quantitative method of real-time reverse transcription polymerase chain assay based ob simulation of polymerase chain reaction kinetics[J].Anal Biochem,2002,302(1):52-59.
[288]张弛宇,徐顺高,黄发祥.一种新颖简便的荧光实时定量RT-PCR相对定量方法的建立[J].生物化学与生物物理进展,2005,32(9):883-888
[289]张立国,张琚.实时定量PCR技术的介绍[J].生物技术,2003,13(2):39-40
[290]Kagi J H R,Hunziker P,Vasak M.Metallothionein:Biochemistry and spatial structure[J].Trace elements in clinical medicine,1990:395-403
[291] Vasak M, Hasler D W. Metallothionein: new functional and structural insights [J].Cur Opin Chem Bio, 2000,4:177-183
[292] Yamada M, Hayashi H, Hozumi I, et al. Subcellular location of growth inhibitory factor in rat brain: Light and electron microscopic immunohistochemical studies [J]. Brain Res, 1996, 735: 257-264
[293] Bremner I. Interaction between metallothionein and trace metals [J]. Progr in Food Nutr Sci, 1987, 11: 1-37
[294] Heinrich P C, Castell J V, Andus T. Interleukin-6 and the acute phase response [J]. Biochem J, 1990,265:621-636
[295]Tamai K T, Liu X, Silar P, et al. Heat shock transcription factor activates yeast metalloth- ionein gene expression in response to heat and glucose starvation via distinct siganlling pathways [J]. Mol Cell Biol, 1994, 141(2): 8155-8165
[296] Durnam D M, Palmiter R D. Transcriptional regulation of the mouse metallothionein I gene by heavy metals [J]. J Biol Chem, 1981, 256: 5712-5716
[297] Palmiter R D. Molecular biology of metallothionein in animal tissues [J]. Eisei Kagaku, 1987, 24: 128-131
[298] Holt D, Magos L, Webb M. The interaction of cadmium-induced rat renal metallothionein with bivalent mercury in vitro [J]. Chem Biol Interact, 1980, 32: 125-135
[299] Park J D, Liu Y, Klaassen C D. Protective effect of metallothionein against the toxicity of cadmium and other metals [J]. Toxicology, 2001, 163: 93-100
[300] Gong Q, Hart B A. Effect of thiols on cadmium-induced expression of metallothionein and other oxidant stress genes in rat lung epithelial cells [J]. Toxicology, 1997, 119(3): 179-191
[2]廖自基.环境中微量重金属元素的污染危害与迁移转化[M].北京:科学出版社,1989,69-97
[3]杨志新,刘树庆.Cd、Zn、Pb单因素及复合污染对土壤酶活性的影响[J].土壤与环境,2000,9(1):15-18
[4]和文祥.土壤酶与重金属关系的研究现状[J].土壤与环境,2000,9(2):139-142
[5]赵春燕,孙军德,宁伟,等.重金属对土壤微生物酶活性的影响[J].土壤通报,2001,32(2):92-94
[6]史长青.重金属污染对水稻土酶活性的影响[J].土壤通报,1995,26(1):34-35
[7]Kandeler E,Lufienegger G,Schwarz S.Influence of heavy metals on the functional diversity of soil microbialcommunities[J].Bilogy and Fertility of Soils,1997,23:299-306
[8]Khan K S,Xie Z M,Huang C Y.Effects of cadmium,lead and zinc on size of m icrobial biomassin red soil[J].Pedo sphere,1998A,8:27-32
[9]张铣,薛彬,魏雪涛,等.镉免疫毒性机理的初步探讨[J].中国环境科学,1999,19(6):530-535
[10]Mukherji S,Maitra P.Toxic effects of lead on growth and metabolism of germinating rice(Oryza salivaL) seedsand mitosis of onion(Allium cepa L)[J].Indian J Exp Biol,1976,14:519-521
[11]秦天才,吴玉树,王焕校,等.镉、铅及其相互作用对小白菜根系生理生态效应的研究[J].生态学报,1998,18(3):320-325
[12]Jarvis J C,Jones L H P,Hopper M J.Cadmium uptake from solution by plants and its transport from roots to shoots[J].Plant Soil,1976,44:179-191
[13]Cataldo D A,Garland T R,Wildung R E.Cadmium uptake kinetics in intact soybean plants[J].Plant Physiol,1983,73(3):844-848
[14]李玉红,宗良纲,黄耀,等.不同有机酸对水稻吸收铅的影响[J].南京农业大学学报,2002,25(3):45-48
[15]孙铁珩主编.污染生态学[M].北京:科学出版社,2001,160-198
[16]王银秋,张迎梅,赵东芹,等.重金属镉、铅、锌对鲫鱼和泥鳅的毒性[J].甘肃科学学报,2003,15(1):35-38
[17]胡家会,张永忠,张培玉,等.铅、铬和硒对玫瑰无须鱼巴毒性的初步研究[J].经济动物学 报,2004,8(3):171-174
[18]陈亮,郭红岩,沈红,等.低浓度铅暴露对鲫鱼肝脏抗氧化系统的影响[J].环境化学,2002,21(5):485-489
[19]Saint Denis M,Labrot F.Olutathione,Olutathione-Related Enzymes and Catalase Activities in the Earth-worm Eisenia fetida andmi[J].Arch Environ Contam Toxicol,1998,35:602-614
[20]刘艳平,李炼,李忠魁,等.底泥重金属铅对鲤鱼红细胞遗传物质的损伤[J].实用预防医学,2003,10(3):333-335
[21]陈怀满主编.土壤-植物系统中的重金属污染[M].北京:科学出版社,1996,210-252
[22]刘宗平主编.动物中毒病学[M].北京:中国农业出版社,2006,394
[23]阮素云,顾祖维,杨勇骥.采用能谱法研究铅对大鼠血脑屏障的通透性[J].中华预防医学杂志,1999,33(2):107-109
[24]赵正言,邵杰,竺智伟.铅的神经毒理机制研究进展[J].中国实用儿科杂志,2006,21(3):163-165
[25]Adhikari N,Sinha N,Narayan R,et al.Lead-induced cell death in tests of young rats[J].J Appl Toxicol,2001,21(4):275-277
[26]李国君,吴德生,李鹏高,等.醋酸铅引起神经细胞的凋亡[J].卫生毒理学杂志,2001,15(3):156-158
[27]李茂进.铅影响学习记忆的研究进展[J].国外医学卫生学分册,2000,27(3):139-143
[28]Kern M,Audesirk G.In organic lead may inhibit neuritis development in cultured rat hippocampal neurons through hyper phosphorlation[J].Toxicol Appl Pharmacol,1995,134(1):111-123
[29]Costa L G,Fox D A.A selective decrease of cholinergic muscarinic receptors in the visual cortex of adult rats following developmental lead exposure[J].Brain Res,1983,276:259-266
[30]Kishi R,Uchino E.Effects of low lead exposure on neuro-behavioral function in the rat[J].Arch Environ Health,1983,38:25-33
[31]Sharifi A M,Shadi B,Masoomeh J,et al.Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo[J].Neuroscience Letters,2002,329:45-48
[32]Rajat Sandhir,Deepinder Julka,Kiran Dip,et al.Lipoperoxidative damage on lead exposure in rat brain and its implication on membrance bound enzymes[J].Toxicol Appl Pharmacol,1994,74:66-71
[33]Adonaylo V N,Oteiza P I.Lead intoxidation:antidant defense and oxidative damage in rat brain [J].Toxicology,1999,135:77-85
[34]丁训诚,刘春芳,董竞武,等.铅对发育中的脑脂质过氧化作用的影响[J].中国药理学与毒理学杂志,1988,2:293-295
[35]Bouton C M,Frelin L P,Forde C E,et al.Synap totagmin I is a molecular target for lead[J].J Neurochem,2001,76:1724-1735
[36]李权武,王建华.动物繁殖毒理学[M].西安:陕西科学技术出版社,1999
[37]孙素玲,于小丹.醋酸铅对小鼠精子形态影响[J].安徽技术师范学院学报,2001,15(4):383-389
[38]周艳,金丹东,袁小倩.铅对小鼠精子形态影响的观察[J].生物通报,2003,38(3):54-55
[39]马保华,史志诚,艾小云,等.醋酸铅对小鼠受精能力及受精卵发育毒性研究[J].西北大学学报(自然科学版),2006,36(1):93-95
[40]J P Bonde,Mjoffe,P Apostoli,et al.Sperm count and chromatin structure in men exposed to inorganic lead:lowest adverse effect levels Occup[J].Environ Med,2002,59:234-242
[41]Susan Benoff,Grace M Centola,Colleen Millan,et al.Increased seminal plasma lead levels adversely affect the fertility prtential of sperm in IVF[J].Hum Reprod,2003,18:374-383
[42]Tohru Kimura,Akira Suzuki,Yukiko Fujita,et al.Conditional loss or PTEN leads to testicular teratoma and enhances embryonic germ cell production[J].Development,2003,130:1691-1700
[43]Suzanne Jackowski,Jerold E Rehg,Yong-Mei Zhang,et al.Disruption of CCTB2 expression leads to gonadal dysfunction[J].Mol Cell Biol,2004,24:4720-4733
[44]Tian L,Lawrence D A.Lead inhibits nitric oxide production in vitro by murine splenic macrophages[J].Toxicol Appl Pharmacol,1995,132:156-163
[45]Fischbein A,Tsang P,Luo J C,et al.Phenotypic aberrations of CD+3 and CD+4 cell and functional impairments of lymphocytes at low-lead occupational exposure to lead[J].Clin Immunol Immunopathol,1996,66:163-168
[46]Heo Y,Parspns P J,Laurence D A.Lead differentially modifies cytokine production in vitro and in vivo[J].Toxicol Appl Pharmacol,1996,138:149-157
[47]Shen X L,Lee K,Konig R.Effects of heavy metal ions on resting and antigen-activated CD~(4+) T cells[J].Toxicology,2001,169:67-80
[48]Krocova Z,M acela A,Kroca M,et al.The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro[J].Toxicol in Vitro,2000,14:33-40
[49]McCabe M J,Singh K P,Reiners J J.Low level lead exposure in vitro stimulates the proliferation and expansion of alloantigen reactive CD~(4+) high T cells[J].Toxicol Appl Pharmacol,2001,177:219-231
[50]Gupta P,Husain M M,Shankar R,et al.Lead exposure enhances virus multiplication and pathogenes is in mice[J].Vet Hum Toxicol,2002,44:205-210
[51]Bishayi B,Sengupta M.Intracellular survival of staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature swiss albino mice[J].Toxicology,2003,184:31-39
[52]李金有.铅致大鼠心肌细胞巯基水平改变与硒对其影响的研究[J].卫生毒理学杂志,1998,12(3):161-162
[53]朱宝立.金属元素对人胚肺细胞联合毒性的研究[J].江苏预防医学,1996(2):3-5
[54]牛静萍.利用大鼠游离肝细胞的生化指标研究金属化合物的联合毒性[J].中国公共卫生学报,1995,14(2):97-99
[55]蔡虹,翁坤荣.矮小身材儿童头发中8种微量元素分析[J].广东微量元素科学,2004,11(1):32-35
[56]刘希兰,陈陵.微量元素与胚胎生长发育[J].微量元素与健康研究,2003,20(3):52-54
[57]薛会灵,秦英,王树松.围产期铅暴露对胎儿神经系统的影响[J].国外医学妇幼保健分册,2005,16(4):206-207
[58]李晓婷.低水平铅暴露对中枢神经系统的毒性作用及其分子机制[J].今日化学,2005,1:55-64
[59]Markovac J,Goldstein G W.Picomolar concentrations of lead stimulate brain protein kinase C[J].Nature,1988,334:712
[60]Peng S,Hajela R K,Atchison W D.Characteristics of block by Pb~(2+) of function of human neuronal L-,N-,and R-type Ca~(2+) channels transiently expressed in human embryonic kidney 293cells[J].Mol Pharmacol,2002,62(6):1418-1430
[61]Perrier J F,Alaburda A,Hounsgaard J.Spinal plasticity mediated by postsynaptic L-type Ca~(2+)channels[J].Brain Res Brain Res Rev,2002,40(123):223-229
[62]Richardt G,Federolf G,Habermann E.Affinity of heavy metal ions to intracellular Ca~(2+)-binding proteins[J].Biochem Pharmacol,1986,35:1331
[63]Habermann E,Crowell K,Janicki P.Lead and other metals can substitute for Ca~(2+) in calmodulin [J].Arch Toxicol,1983,54:61
[64]Cheung W Y.Calmodulin:Its potential role in cell proliferation and metal toxicity[J].Fed proc,1984,43:2995
[65]孙黎光,邢伟,刘素媛,等.铅对大鼠脑海马神经细胞Ca~(2+)浓度及蛋白激酶C活性的影响[J].卫生毒理学杂志,1997,37:180
[66]Toscano C D,Hashemzadeh Gargari H,McGlothan J L,et al.Developmental Pb~(2+) exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain[J].Brain Res Dev Brain Res,2002,139:217-226
[67]Kandel E R.The molecular biology of memory storage:a dialogue between genes and synapses[J].Science,2001,294:1030-1038
[68]Nihei M K,Desmond N L,McGlothan J L,et al.N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning[J].Neuroscience,2000,99:233-242
[69]Guilarte T R,McGlothan J L.Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb~(2+)-exposed rats:implications for synaptic targeting and cell surface expression of NMDAR complexes[J].Brain Res Mol Brain Res,2003,113(122):37-43
[70]Zhang X Y,Liu A P,Ruan D Y,et al.Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNAs in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry[J].Neurotoxicol Teratol,2002,24(2):149-160
[71]Reddy G R,Basha M R,Devi C B,et al.Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat[J].Int J Dev Neurosci,2003,21(6):347-352
[72]董桂娟,赵正言,竺智伟.铅暴露对生长发育期大鼠不同脑区一氧化氮合酶活力的影响[J].中华劳动卫生职业病杂志,2003,21(4):263-265
[73]Zhu Z W,Yang R L,Dong G J,et al.Study on the neurotoxic effects of low-level lead exposure in rats[J].J Zhejiang Univ Sci,2005,6(7):686-692
[74]余绍蕾,蔡宇.枸杞多糖对染铅小鼠海马区NO和NOS活性的影响[J].中药药理与临床,2006,22(1):41-42
[75]Chetty C S,Reddy G R,Murthy K S,et al.Perinatal lead exposure alters the expression of neuronal nitric oxide synthase in rat brain[J].Int J Toxicol,2001,20(3):113-120
[76]王韵,韩济生.一氧化氮在医学中的现在和将米[J].生理科学进展,1999,30(1):94-95
[77]王静,李积胜,张进,等.铅对小鼠海马一氧化氮合酶活力及表达的影响[J].中华劳动卫生职业病杂志,2000,18(4):204-206
[78]Savolainen K M,Loikkanen J,Eerikainen S,et al.Interactions of excitatory neurotransmitters and xenobiotics in excitotoxicity and oxidative stress:glutamate and lead[J].Toxicol Lett,1998,102:363
[79]牛玉杰,张荣,程云会,等.醋酸铅对小鼠脑细胞凋亡及Bcl-2、bax基因表达的影响[J].中华预防医学杂志,2002,36(1):30-33
[80]文涛,孙黎光,彭博.慢性铅暴露小鼠脑海马c-fos、c-jun表达与学习记忆的关系[J].毒理学杂志,2005,19(3):236
[81]蔡宇,余绍蕾,张荣华.枸杞多糖对染铅小鼠行为功能保护及脑细胞Fas抗原表达的影响[J].环境与职业医学,2005,22(6):533-534
[82]Stohs S J,Bagchi D.Oxidative mechanisms in the toxicity of metal ions[J].Free Radic Biol Med,1995,18:321-336
[83]陆新华,刘卓宝.自由基与铅中毒机制的研究进展[J].中华劳动卫生职业病杂志,1998,16(3):189-191
[84]陆巍.铅的神经毒作用机制[J].国外医学卫生学分册,1995,22:341-343
[85]王桂芝,刘双年,候玉春,等.铅对大鼠脑细胞脂质过氧化及超氧物歧化酶活性的影响[J].卫生毒理学杂志,1995,9:175
[86]Winder C,Bonin T.The genotoxicity of lead[J].Mutation Res,1993,285(1):117-124
[87]Hartwig A.Interactions by carcinogenic metal compounds with DNA repair processes:toxicological implications[J].Toxicol Lett,2002,127(1-3):47-54
[88]Restrepo H G,Sicard D,Torres M M.DNA damage and repair in cells of lead exposed people[J].Am J Ind Med,2000,38(3):330-334
[89]Razmiafshari M,Kao J,d'Avignon A,et al.NMR identification of heavy metal-binding sites in a synthetic zinc finger peptide:toxicological implications for the interactions of xenobiotic metals with zinc finger proteins[J].Toxicol Appl Pharmacol,2001,172(1):1-10
[90]Quintanilla-Vega B,Hoover D J,Bal W,et al.Lead interaction with human protamine(HP2) as a mechanism of male reproductive toxicity[J].Chem Res Toxicol,2000,13(7):594-600
[91]Rydberg B.Radiation-induced DNA damage and chromatin structure[J].Acta Oncol,2001,40(6):682-685.
[92]GB16297-1996,中华人民共和国国家标准大气污染物综合排放标准[S].北京:国家环境保护局,1996
[93]GB 3838-2002,中华人民共和国地表水环境质量标准[S].北京:中国环境科学出版社出版,2002
[94]天津大学图书馆.环境科学与工程学科信息数据库[DB/OL]http://202.113.6.254/hi/web,2003-3-25
[95]赵璇,吴天宝.我国饮用水源的重金属污染及治理技术深化问题[J]_给水排水,1998,24(10):22-25
[96]邹国良.保护土壤环境是我们的历史责任[J].中国科学报,1989年1月10日第1版
[97]周锡爵.张士灌区镉污染及其解决和利用的途径[J].农业环境保护,1987,6(2):17-19
[98]刘立群.赣南土壤污染的防治途径[J].资源开发与保护杂志,1990,6(2):100-102
[99]王江平.入世后高浓度磷肥中镉的问题[J].磷肥与复肥,2002,17(5):11-15
[100]Research Triangle Institute.Toxicological profile for cadmium[R].Prepared for U.S.Agency for Toxic Substances and Disease Registry,July 1999
[101]王夔主编.生命科学中的微量元素(第二版)[M].北京:中国计量出版社,1996,7:850-882
[102]江中良,王立强,李青旺,等.镉对哺乳动物繁殖性能的影响[J].四川畜牧兽医,2002,29(1):29
[103]Kotsonis F N,Klaassen C D.Toxicity and distribution of cadmium administration to rats at sublethal doses[J].Toxicol Appl Pharmacol,1977,46(1):39-54
[104]Kotsonis F N,Klaassen C D.The relationship of metallothionein to the toxicity of cadmium after prolonged oral administration to rats[J].Toxicol Appl Pharmacol,1978,46(1):39-54
[105]Sato K,Iwamasa T,Tsuru T,et al.An ultrastructural study of chronic cadmium chloride-induced neuropathy[J].Acta Neuropathol(Berl),1978,41(3):185-190
[106]Murthy R C,Saxena D K,Lal B,et al.Chronic cadmium-ethanol administration alters metal distribution and some biochemicals in rat brain[J].Biochem Int,1989,19(1):135-143
[107]Valois A A,Webster W S.The choriod plexus as a target site for cadmium toxicity following chronic exposure in the adult mouse:An ultrastructural study[J].Toxicology,1989,55:193-205
[108]刘伟成,李明云.镉毒性毒理学研究进展[J].广东微量元素科学,2005,12(12):1-5
[109]刘利娟,丁雄,唐玲,等.锌、镉与儿童中枢神经系统疾病51例分析[J].微量元素与健康研究,1994,11(4):59
[110]马军,斯欣,叶广俊.环境镉污染对儿童学习记忆的影响[J].中国学校卫生,2000,21(6):440-441
[111]戈果,王景传,许庭良,等.V_E对慢性镉中毒小鼠黑质神经元的保护作用[J].中国地方病学杂志,2002,21(6):450-452
[112]李湘鸣,居中华,孙蓉,等.镉对大鼠睾丸中某些酶活性及组织形态的影响[J].卫生毒理学杂志,1999,13(1):31-33
[113]李建秀,王晓梅.氯化镉对小鼠精子的影响[J].工业卫生与职业病,1997,23(4):213-214
[114]Saygi S,Deniz G,Kutsal O,et al.Chronic effects of cadmium on kidney,liver,testis,and fertility of male rats[J].Biol Trace Elem Res,1991,31(3):209-214
[115]Mohan J,Moudgal R P,Panda J N.Effects of cadmium salt on phosphomonoesterases activity and fertilizing ability of fowl spermatozoa[J].Indian J Exp Biol,1992,30(3):241-243
[116]杨建明,陈琼宇,曾祥斌,等.镉对雄性生育功能的影响[J].中国公共卫生,2000,1(4):313-314
[117]Machemer L,Lorke D.Embryotoxic effect of cadmium on rats upon oral administration[J].Toxicol Appl Pharmacol,1981,58:438-443
[118]Levin A A,Miller R K.Fetal toxicity of cadmium in the rat:decreased utero-placental blood flow [J].Toxicol Appl Pharmacol,1981,58(2):297-306
[119]庞惠民,朱玉琢,刘念稚.益母草对硫酸镉诱发的小鼠骨髓细胞微核率的影响[J].吉林大学学报(医学版),2002,28(5):463-464
[120]Lafuente A,Blanco A,Marquez N,et al.Effects of acute and subchronic cadmium administration on pituitary hormone secretion in rat.[J].Rev Esp Fisiol,1997,53(3):265-269
[121]Esquifino A I,Marquez N,Alvarez Demanuel E,et al.Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats[J].J Trace Elements Med Biol,1999,12(4):205-210
[122]曾祥斌,金泰,周袁芬,等.镉对大鼠血清性激素水平的影响[J].中华劳动卫生职业病杂志,2001,19(6):430-432
[123]张文昌,吴志仁,李煌元,等.染镉雌性大鼠垂体、卵巢对性腺激素的反应机能状况[J].卫生毒理学杂志,2002,16(1):24-26
[124]Blakley B R.Humoral immunity in aged mice exposed to cadmium[J].Can J Vet Res,1988,52(2):291-292
[125] Exon J H, Koller L D, Kerkvliet N I. Tissue residues, pathology and viral-induced mortality in mice chronically exposed to different cadmium salts [J]. J Environ Pathol Toxicol Oncol, 1986, 7(1-2): 109-114
[126] Blakley B R. The effect of cadmium chloride on the immune response in mice [J]. Can J Comp Med, 1985,49(1): 104-108
[127] Blakley B R. The effect of cadmium on chemical- and viral-induced tumor production in mice [J]. J Appl Toxicol, 1986, 6(6): 425-429
[128] Chopra R K, Prasad R, Sharma N, et al. Effect of dietary chronic cadmium exposure on cell-mediated immune response in Rhesus monkeys (Macaca mulatta): Role of calcium deficiency [J]. Arch Toxicol, 1984, 56(2): 128-131
[129] Stacey N H, Craig G, Muller L. Effects of cadmium on natural killer and killer cell functions in vivo [J]. Environ Res, 1988, 45(1): 71-77
[130] Daniels M J, Menache M G, Burleson G R,et al. Effects of NiCl_2 and CdCl_2 on susceptibility to murine cytomegalovirus and virus-augmented natural killer cell and interferon responses [J]. Fundam Appl Toxicol, 1987, 8(4): 443-453
[131] Stacey N H. Effects of cadmium and zinc on spontaneous and antibody-dependent cell- mediated cytotoxicity [J]. J Toxicol Environ Health, 1986, 18(2): 293-300
[132] Prigge E. Early signs of oral and inhalative cadmium uptake in rats [J]. Arch Toxicol, 1978, 40(3): 231-247
[133] Groten J P, Sinkeldam E L, Luten J B, et al. Comparison of the toxicity of inorganic and liver-incorporated cadmium: A 4-week feeding study in rats [J]. Food Chem Toxicol, 1990,28(6): 435-441
[134] Masaoka T, Akahori F, Arai S, et al. A nine-year chronic toxicity study of cadmium ingestion in monkeys. I. Effects of dietary cadmium on the general health of monkeys [J]. Vet Hum Toxicol, 1994,36(3): 189-194
[135] Hays E S, Marga retten N. Long-term oral cadmium produces bone marrow hypoplasia in mice [J]. Exp Hematol, 1985, 13(3): 229-234
[136] Sakata S, Iwami K, Enoki Y, et al. Effects of cadmium on in vitro and in vivo erythropoiesis: Erythroid progenitor cells (CFU-E) iron, and erythropoietin in cadmium-induced iron deficiency anemia [J]. Exp Hematol, 1988, 16(7): 581-587
[137]Wilson R H,DeEds F,Cox A J.Effects of continued cadmium feeding[J].J Pharmacol Exp Therap,1941,71:222-235
[138]Schroeder H A.Cadmium as a factor in hypertension[J].J Chronic Dis,1965,18:647-656
[139]Jamall I S,Naik M,Sprowls J J,et al.A comparison of the effects of dietary cadmium on heart and kidney oxidant enzymes:Evidence for the greater vulnerability of the heart to cadmium toxicity[J].JAppl Toxicol,1989,9:339-345
[140]王强,姚素梅,郭秀珍.急性镉中毒大鼠致死时重要器官的镉分布[J].广东微量元素科学,1998,5(9):23-26
[141]Shigematsu I.The epidemiological approach to cadmium pollution in Japan[J].Ann Acad Med Singapore,1984,13:231-236
[142]Nogawa K,Tsuritani I,Kido T,et al.Serum vitamin D metabolites in cadmium-exposed persons with renal damage[J].Int Arch Occup Environ Health,1990,62:189-193
[143]Buchet J P,Lauwerys R,Roels H,et al.Renal effects of cadmium body burden of the general population[J].Lancet,1990,336:699-702
[144]刘杰.镉的毒性和毒理学研究进展[J].中华劳动卫生职业病杂志,1999,16(1):2-4
[145]Carageorgiou H,Tzotzes V,Pantos C,et al.In vivo and in vitro effects of cadmiumon adult rat brain total antioxidant status,acetylcholinesterase,(Na~+,K~+) ATPase and Mg~(2+)ATPase activities:protection by L-cysteine[J].Basic Clin Pharmacol Toxicol,2004,94(3):112-118
[146]Faurakov B,Bjerregaard H F.Evidence for cadmium mobilization of intra cellular calcium through a divalent cation receptor in renal distal epithelial A6 cells[J].Pflugers Arch,2002,445(1):40-50
[147]Gadbut A P,Cash S A,Noble J A,et al.The effect of Ca~(2+) channel antagonists(Cadmium,omega-conotoxin GIVA,and nitrendipine) on the release of angiotensin Ⅱ from fetal rat brain in vitro[J].Neurosci Lett,1991,123(1):91-94
[148]Dudel J,Pamas H,Parnas I.Evoked phasic release in frog nerve terminals obtained after block of Ca~(2+) entry by Cd~(2+)[J].Pflugers Arch,1991,419(2):197-204
[149]Smith J B,Dwyer S D,Smith L,et al.Cadmium evokes ino sitol polyphosphate formation and calcium mobilization[J].J Biol Chem,1989,264:7115
[150]马军,斯欣,叶广俊.镉对神经细胞内游离钙浓度的影响[J].中国公共卫生学报,1996,15(1):21-23
[151]Blazka M E,Shaikh Z A.Difference in cadmium and mercury uptakes by hepatocytes:Role of calcium channels[J].Toxicol Appl Pharmacol,1991,110:355-363
[152]Yang C F,Shen H M,Shen Y,et al.Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts(MRC-5cells)[J].Environ Health Perspect,1997,105:712-716
[153]Muller L.Consequences of cadmium toxicity in rat hepatocytes mitochondrial dysfunction and lipid peroxidation[J].Toxicology,1991,40:285
[154]Bagchi D,Vuchetich P J,Bagchi M.Induction of oxidative stress by chronic administration of sodiumdi-chromate[chromium Ⅵ]and cadmium chloride[cadmium]to rats[J].Free Radic Biol Med,1997,22(3):471-478
[155]Karmakar R,Roy S,Chatterjee M.The effects of cadmium on the hepatic and renal levels of reduced glutathione,the activity of glutathione S-transferase and gamma glutamyl transpeptidase [J].J Environ Pathol Toxicol Oncol,1999,18(1):29-35
[156]Shukla A,Shukla G S,Srimal R C.Cadmium-induced alterations in blood-brain barrier permeability and its possible correlation with decreased micro vessel antioxidant potential in rat [J].Hum ExpToxicol,1996,15(5):400-405
[157]Briehl M M,Baker A F.Modulation of the antioxidant defense as a factor in apoptosis[J].Cell Death Different,1996,3:63-70
[158]Hart B A,Enema J D,Potts R J,et al.Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells and its potential involvement in cadmium carcinogenesis[J].Toxicology,2000,147:215-228
[159]余日安,陈学敏.镉对大鼠肝细胞原癌基因c-fos、c-jun表达的影响[J].卫生研究,2000,29(6):364-365
[160]余日安,陈学敏.镉对大鼠肝细胞原癌基因c-myc表达的影响[J].中国公共卫生,2000,16(11):995-996
[161]Margoshes M,Vallee B L.A cadmium protein from equine kidney cortex[J].J Amer Chem Soc,1957,(79):4813
[162]Quafe C J,Findley S D,Ericksin J C,et al.Induction of new metallothione in isoform(MT-2)occurs during differentiation of stratified squamous epithelia[J].Biochemistry,1994,33:7250-7259
[163]McKenna I M,Bare R M,Waalkes M R Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium[J].Toxicology,1996,107(2):121-130
[164]任宏伟,茹炳根.金属硫蛋白(Metallothionein,MT)基因在转基因领域的应用[J].生物工程进展,2000,20(4):35-39
[165]张博润,蔡向荣,怀文辉,等.金属硫蛋白的研究进展及应用前景[J].微生物学报,1999,26(5):355-357
[166]Cherian M G,Goyer R A.Metallothioneins and their role in the metabolism and toxicity of metals[J].Life Sci,1978,23(1):1-9
[167]Emily F M,Brunce A F.Mechanisms of nephrotoxicity from metal combinations:a review[J].Drug Chem Toxicol,2000,23(1):1-12
[168]Karpela A,Louenira R,Yrjanheikki E,et al.Lead and cadmium concentrations in maternal and umbilical cord blood,amniotic fluid,placenta,an amniotic membranes[J].Ann J Obstet Gynecol,1986,155,1086-1089
[169]Antonio M T,Corpas I.,Leret M L.Neurochemical changes in newborn rat's brain after gestational cadmium and lead exposure[J].Toxicol Lett,1999,104,1-9
[170]刘艳虹.铅对儿童神经系统毒性作用的研究进展[J].中国特殊教育,2006,67(1):62-65
[171]A Pillai L,Priya S Gupta.Effects of combined exposure to lead and cadmium on the hypothalamic-pituitary axis function in proestrous rats[J].Food Chem Toxicol,2003,41:379-384
[172]Lynch G P,Smith D F,Fisher M,et al.Physiological responses of calves to cadmium and lead[J].J Anita Sci,1976,42,410-421
[173]Burrows,G.E.,Borchard,R.E.Experimental lead toxicosis in ponies:Comparison of the effects of smeiler effluents,contaminated hay and lead acetate[J].Am J Vet Res,1982,43,2129-2133
[174]Mihaud G E,Mehennaoui S.Indicaters of lead,Zinc and cadmium in cattle.I.Results in a polluted area[J].Vet Hum Toxicol,1988,30(6):513-517
[175]Cibulka J,Miholova D,Pi sa J,et al.Natural levels of lead,cadmium and mercury in tissues and hair of newborn calves from different areas of czechoslovakia[J].Sci total environ,1989,84:101-112
[176]刘宗平,马卓,李文范,等.铅镉中毒发病机理的研究-绵羊动物模型的复制[J].中国兽医科技,1996,26(10):11-14
[177]王学谦,尹先仁,白雪涛.铅镉联合作用对大鼠肾小管上皮细胞脂质过氧化的影响[J].卫 生研究,2002,31(4):232-234
[178]Patricia Bizarro,Sandra Acevedo,Geraldine Nino-Cabrera,et al.Ultrastructural modifications in the mitochondrion of mouse Sertoli cells after inhalation of lead,cadmium or lead-cadmium mixture[J].Reprod Toxicol,2003,17,561-566
[179]王兰,杨秀清,王茜,等.镉在河蟹五种组织器官的积累及对酯酶同工酶的影响[J].动物学报,2001,47(专刊):96-100
[180]陈卫平,刘世杰.铅的肾细胞毒性及锌的保护作用[J].卫生毒理学杂志,1995,9(2):73-76
[181]马卓,刘宗平,张白银,等.绵羊铅镉联合中毒与硒解毒的试验病理学研究[J].中国兽医科技,1997,27(3):12-14
[182]Liu Z P.Lead poisoning combined with cadmium in sheep and horses in the vicinity of non-ferrous metal smelters[J],The Science of the Total Environment,2003,309:117-126
[183]Nation J R,Frye G D,VonStultz J,et al.Effects of combined lead and cadmium exposure:changes in schedule-controlled responding and in dopamine,serotonin and their metabolites[J].Behav Neurosci,1989,103(5):1108-1114
[184]Nation J R,Grover C A,Bratton G R,Salinas J A.Behavioural antagonism between lead and cadmium[J].Neurotoxicol Teratol,1990,12:99-104
[185]Mahaffey K R,Caper S G,Gladen B C,et al.Concurrent exposure to lead,cadmium and arsenic [J].J Lab Clin Med,1981,98:463-480
[186]Haneef S S,Swarup D,Dwivedi S K,et al.Effects of concurrent exposure to lead and cadmium on renal function in goats[J].Small Rumin Res,1998,28,257-261
[187]Nolan C V,Shaikh Z A.Lead nephrotoxicity and associated disorders:Biochemical mechanism [J].Toxicol,1992,73:127-146
[188]Anilkumar Pillail,Sarita Gupta.Effect of gestational and lactational exposure to lead and/or cadmium on reproductive performance and hepatic oestradiol metabolizing enzymes[J].Toxicol Lett,2005,155:179-186
[189]金建年,彭文娟,彭兆麟.痰净雾化液超声雾化吸入祛痰作用研究[J].湖北中医杂志,1999,21(4):157
[190]李长生,杨炯,李清泉,等.乙酰半胱氨酸胶囊止咳祛痰作用的临床研究[J].中国医院药学杂志,1999,19(11):676
[191]Gregory S,Kelly N D.Clinical Applications of N-acetylcysteine[J].Altern Med Rev,1998,3: 114
[192]代心平.N-乙酰半胱氨酸药理与保健作用研究[J].海南医学,2004,12(10):121-122
[193]Lailey A F.Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats[J].Hum ExpToxicol,1997,16:212-216
[194]王雨,徐兆发,喻道军,等.N-乙酰半胱氨酸和亚硒酸钠对镉亚慢性毒性的影响[J].毒理学杂志,2005,19(4):251-253
[195]Ueland P M,Mansoor M A,Guttormsen A B,et al.Reduced oxidized and protein-bound forms of homocysteine and other aminothiol in plasma comprise the redox thiol status—a possible element of the extracelluar antioxidant defense system[J].J Nutr,1996,126(4Suppl):1281
[196]Labib R,Abdel-Rahman M,Turkall R.N-acetvlcvsteine pretreatment decreases cocaine and endotoxin-induced hepatotoxicity[J].J toxicol environ health,2003,66(3):223-239
[197]Buhimschi L A,Buhimschi C S,Weiner C P.Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation[J].Am J obstet gynecol,2003,188(1):203-208
[198]Allegra L,Dal Sasso M,Bovio C,et al.Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations[J].Arzneimittelforschung,2002,52(9):669-676
[199]Dick C A,Brown D M,Donaldson K.The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types[J].Inhat Toxicol,2003,15(1):39-52
[200]Cammer W.Protection of cultured oligodendrocytes against tumor necrosis factor-alpha by the antioxidants coenzyme Q(10) and N-acetylcysteine[J].Brain Res Bull,2002,58(6):587-592
[201]Malins D C,Hellstrom K E,Anderson K M.Antioxidant-induced changes in oxidized DNA[J].Proc Natl Acad Sci USA,2002,99(9):5937-5941
[202]Recchioni R,Marcheselli F,Moroni F,et al.Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by N-acetyl-L-cysteine[J].Metabolism,2002,51(11):1384-1388
[203]De Flora S,Izzotti A,D'Agostini F,et al.Mechanism of N-acetylcysteine in the prevention of DNA damage and cancer,with special reference to smoking-related end-points[J].Carcinogenesis,2001,22(7):999
[204]Srianujata S.Lead-the toxic metal to stay with human[J].J Toxicol Sci,1998,23(2):237-240
[205]童建,冯致英.环境化学物的联合毒性作用[M].上海:上海科学技术文献出版社,1994,1
[206]洪庆涛,唐一鹏.新生大鼠大脑皮层神经细胞的体外原代培养[J].神经解剖学杂志,1994,10(3):259-261
[207]Davis G E,Manthorpe M,Williams L R,et al.Characterization of a laminin-containing neurite-promoting factor and a neuronotrophic factor from peripheral nerve and related sources [J].Ann N Y Acad Sci,1986,486:194-205
[208]Scortegagna M,Hanbauer I.The effect of lead exposure and serum deprivation on mesencephalic primary cultures[J].Neurotoxicology,1997,18(2):331-340
[209]Nakai J.Dissociated dorsal root ganglia in tissue culture[J].Am J Anat,1956,99:81-129
[210]Koh J Y,Choi D W.Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay[J].J Neurosci Methods,1987,20:83-90
[211]Mandell J W,Banker G A.Selective blockade of axonogenesis in cultured hippocampal neurons by the tyrosine phosphatase inhibitor orthovanadate[J].J Neurobiol,1988,35:17-28
[212]罗湘颖,杨志敏,王廷华.胎鼠大脑皮质神经元的体外培养及鉴定[J].神经解剖学杂志,2004,20(5):505-508
[213]赵林普,肖定华,陈士英.脑神经细胞的培养[J].生理科学,1983,3:8-9
[214]Silva R F M,Falcao A S,Fernandes A,et al.Dissociated primary nerve cell cultures as models for assessment of neurotoxicity[J].Toxicol Lett,2006,163:1-9
[215]Katharine M W,Haberstroh,Carolyn M Kapron.Activation of c-Jun N-terminal kinase by cadmium in mouse embryo neural cells in vitro[J].Environ Toxicol Pharmacol,2006,22:1-7
[216]吴希如.哺乳动物胚胎神经细胞原代分离性单层培养及其应用[J].生理科学进展,1984,15(3):25
[2171 郑肇青,张宇,张策.探讨单细胞记录和神经细胞培养时神经元的分离方法[J].山西医科大学学报.2005,36(4):516-518
[218]鄂征主编.组织培养技术及其在医学研究中的应用[M].北京:中国协和医科大学出版社,2004,65-69
[219]潘永英,彭书岐,赵一凡,等.大鼠海马神经元的原代无血清培养及鉴定[J].实用医学杂志,2006,22(7):758-759
[220]Brewer G J,Torricelli J R,Evege E K,et al.Optimized survival of hippocampal neurons in B27-supplemented neuronbasal,a new serum-free medium combination[J].J Neurosci Res,1993,35(5):567-576
[221]丁爱石,王富庄.新生大鼠海马神经元在无血清培养液中的生长特性[J].细胞生物学杂志,1993,15(2):88-90
[222]McKinney J S,Willoughby K A,Liang S,et al.Stretch-induced injury of cultured neuronal,glial,and endothelial cell.Effect of polyethylene glycol-conjugated superoxide dismutase[J].Stroke,1996,27:934-940
[223]Hayashi K,Kawai-Hirai R,Ishikawa K,et al.Reversal of neuronal polarity characterized by conversion of dendrites into axons in neonatal rat cortical neurons in vitro[J].Neuroscience,2002,110:7-17
[224]宋岳涛,洪庆涛,唐一鹏.阿糖胞苷对原代培养的大鼠大脑皮质神经元的影响[J].解剖学杂志,2004,27(6):696-699
[225]Muller H W,Seifert W.A neurotrophic factor(NTF) released from primary glial cultures supports survival and fiber outgrowth of cultured hippocampal neurons[J].J Neurosci Res,1982,8:195-204
[226]Muller H W,Beckh S,Seifert W.Neurotrophic factor for central neurons[J].Proc Natl Acad Sci USA,1984,81:1284-1292
[227]邵延坤,王溪原,于越晖,等.乳鼠皮质神经元原代培养与观察[J].吉林医学,2003,24(2):103-104
[228]晏雪生,彭亚琴,民安萍.人胚大脑皮层神经元细胞体外培养方法的建立[J].中国自然医学杂志,2002,4(4):225-226
[229]曾可斌,胡长林,陈阳美.大鼠海马神经元培养与鉴定[J].基础医学与临床,2004,24(5):574-577
[230]胡前胜,董胜璋,陈学敏,等.低剂量铅对原代培养的海马神经元的影响[J].中国公共卫生,2003,19(5):518-520
[231]杨烽,李积胜,杨芳.不同浓度醋酸铅对大鼠原代培养大脑皮层神经元的影响[J].中华劳动卫生职业病杂志,2004,22(3):217-218
[232]陈军,祝卫国,陈秋生,等.铅对体外培养大鼠海马神经细胞生长和Oct-2蛋白表达的影响[J].中华预防医学杂志,2004,38(3):151-153
[233]Prozialeck W C,Grunwald G B,Dey P M,et al.Cadherins and NCAM as potential targets in metal toxicity[J].Toxicol Appl Pharmacol,2002,182:255-265
[234]Shabani A,Rabbani A.Lead nitrate induced apoptosis in alveolar Macrophages from rat lung [J].Toxicology,2000,149(2-3):109-114
[235]De la Fuente H,Portales-Perez D,Baranda L,et al.Effects of arsenic,cadmium and lead on the induction of apoptosis of normal human mononuclear cells[J].Clin Exp Immunol,2002,129(1):69-77
[236]程云会,牛玉杰,张荣,等.醋酸铅对大鼠脑细胞凋亡及对Fas抗原表达的影响[J].卫生毒理学杂志,2002,16(4):226-227
[237]Huxtable.R J.Physiological Action of Taurine[J].J Physiol Revi,1992,72(1):101-142
[238]Kelly S A,Havrilla C M,Brady T C,et al.Oxidative stress in toxicology:established mammalian and emerging piscine model systems[J].Environ Health Perspect,1998,106(7):375-384
[239]Findel T,Holbrook N J.Oxidants,oxidative stress and the bilolgy of aging[J],Nature,2000,408:239-247
[240]孙存普,张建中,段绍瑾.自由基生物学导论[M].合肥:中国科学技术大学出版社,1999,150-156
[241]Cobson K B.The interaction of cadmium and certain other metal ions with proteins and nucleic acids[J].Toxicology,1980,16:1-37
[242]蔡原,姜厚波,张颖花,等.铅对大鼠肾脏的脂质过氧化作用[J].中国医科大学学报,1994,23(6):21-23
[243]孔繁翔.环境生物学[M].北京:高教出版社,2000,68
[244]王维娜,王安利,孙儒泳.水环境中的铜锌铁钴离子对日本沼虾消化酶和碱性磷酸酶的影响[J].动物学报,2001,47(专刊):72-77
[245]Sieg D J,Billings R E.Lead/Cytokine-mediated oxidative DNA damage in cultured mouse hepatocytes[J].Toxicol Appl Pharmacol,1997,142:106-115
[246]Sies H.Glutathione disulfide(GSSG) effiux from cells and tissues[J].Methods Enzymol,1984,105:445-451
[247]程元恺.谷胱甘肽的解毒作用与毒物代谢物[J].生物化学与生物物理进展,1994,21(5):395-399
[248]Gillissen A,Scharling B,Jaworska M,et al.Oxidant scavenge function of ambroxol in vitro:a comparison with N-Acety leysteine[J].Res Exp Med,1997,196:389-393
[249]殷宪敏,杨明峰,刘瑞锁.N-乙酰-L-半胱氨酸对缺氧新生大鼠脑保护作用的研究[J].中华儿科杂志,2001,39(9):566
[250]Flora G J S,Seth P K.Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dhydratase,glutathione and lipid peroxidation during acute lead-ethanol administration in mice [J].Alcohol,1999,18:103-108
[251]周宜灿,陈晓春,朱元贵,等.N-乙酰半胱氨酸防止帕金森病鼠黑质神经元凋亡[J].中国神经科学杂志,2003,19(6):384-388
[252]Bradbury M W,Deane R.Permeability of the blood-brain barrier to lead[J].Neurotoxicology,1993,14:131-136
[253]Agodi A,Viola M,Alberghina M,et al.Effect of low dose lead acetate exposure on the metabolism of nucleic acids and hippocampus of rat during postnanal development[J].Neurosci Res,1990,25:131-137
[254]Huseman C A,Moriarty C R,Angle C K.Childhood lead toxicity and impaired release of thyotropin stimulation hormone[J].Environ Res,1987,42(2):524-533
[255]Eck P C,Wilson L.Toxic Metals in Human Health and Disease[M].Eck Institute of Applied Nutrition and Bioenergetics;1989
[256]Roels H A,Hoet P,Lison D.Usefulness of biomarkers of exposure to inorganic mercury,lead,or cadmium in controlling occupational and environmental risks of nephrotoxicity[J].Ren Fail,1999,21(3-4):251-262
[257]Osterloh J D,Selby J V,Bernard B P,et al.Body burdens of lead in hypertensive nephropathy[J].Arch Environ Health,1989,44(5):304-310
[258]李晔.碘·生命·健康[M].北京:科学出版社,1998,2
[259]郭宝林,贾志海,张玉枝.畜禽铜营养研究进展[J].饲料工业,2005,26(10):48-51
[260]颜世铭,熊丽萍.元素间的相互影响[J].广东微量元素科学,2000,7(11):1-6
[261]曹盛丰,杨丽娥.高碘高铁日粮对产蛋母鸡代谢酶活力和蛋营养成分的影响[J].饲料博览,2000,13(6):5
[262]Cao J,Luo X G.Effect of dietary iron on concentration,age,and length of iron feeding on feed intake and tissue iron concentration of broiler chicks for use as bioassay of supplemental iron sources[J].Poult Sci,1996,75:495
[263]王俊改,马军,吴南屏,等.硒与镉对小鼠肝、肾睾丸组织脂质过氧化作用的交互影响[J]. 中国公共卫生学报,1997,16(1):37-38
[264]Cooper,G P,Manalis,R S.Interaction of lead and cadmium on acetylcholine release at the frog neuromuscular junction[J].Toxicol Appl Pharmacol,1984,74,411-416
[265]张卓然主编.培养细胞学与细胞培养技术[M].上海:上海科学技术出版社,2004,310.
[266]Heid C A,Stevens J,Livak J K,et al.Real time quantitative PCR[J].Genome Res,1996,6(10):986-994
[267]Livak K J,Schittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J].Methods,2001,25:402-408
[268]Hiquchi R,Fockler C,Dollinqer G,et al.Kinetic PCR analysis:real-time monitoring of DNA amplification reactions[J].Biotechnology(N Y),1993,11(9):1026-1030
[269]Ke L D,Chen Z,Yung W K.A reliability test of standard-based quantitative PCR:exogenous standards[J].Mol Cell Probes,2000,14(2):127
[270]Becker K D Pan,Whitely C B.Real-time quantitative polymerase chain reaction to assess gene transfer[J].Hum Gene Ther,1999,10:2559
[271]Higgins J A,Ezzell J,Hinnebusch B J,et al.5' nuclease PCR assay to detect Yersinia pestis[J].J Clin Microbiol,1998,36(8):2284-2288
[272]Bustin S A.Absolute quantitation of mRNA using real-time reverse ranscription polymerase chain reaction assays[J].J Mol Endocrinol,2000,25:169-193
[273]Anderson A J,Pike C J,Cotman C W,et al.Differential induction of immediate early gene proteins in cultured neurons by beta-amyloid(A beta):association c-jun with A beta-induced apoptosis[J].Neurochem,1995,65:1487-1498
[274]周伟,吴圣楣,陈惠全.Bcl-2,Bax mRNA在新生大鼠缺血缺氧后的表达及其与脑细胞凋亡的关系[J].新生儿杂志,2001,16(2):69-72
[275]Marina Nedelcheva,Tanya Topouzova,Ginka Genova.Transcription of Dfos is stimulated by brain tumours of l(2)gl-deficient larvae of drosophila melanogaster[J].Int J Biochem Cell Biol,2001,33(1):45-51
[276]程金平,王文华,贾金平.氯化甲基汞对大鼠海马c-jun蛋白表达的影响[J].中国环境科学,2003,23(4):431-434
[277]程金平,王文华,贾金平.氯化甲基汞对大鼠脑c-fos、c-jun基因表达的影响[J].环境科学,2003,24(1):52-56
[278]Stephenson C P,Hunt G E,Topple A N,et al.The distribution of 3,4-methylenedioxymet ha-mphetamine ecstasy induced c-fos expression in rat brain[J].Neuroscience,1999,92(3):1011-1023
[279]Moore J,Boswell S,Hoffman R,et al.Mutant H-ras over-expression inhibits a random apoptotic nuclease in myeloid leukemia cells[J].Leukemia Res,1993,17:703-709
[280]Gonzalez-Martin C,de Diego I,Crespo D,et al.Transient C-fos expression accompanies naturally cell death in the developing interbem ispheric cortex of the rat Brain[J].Res Dev Brain Res,1992,68(1):83-95
[281]Chen S C,Curran T,Morgan J I.Apoptosis in the nervous system:new revelations[J].Clin Pathol,1995,48(1):7-12
[282]Hu L,Hatano M,Ruther U,et al.Overexpression of c-fos induces apoptosis of CD43+ pro-B cells[J].J Immunol,1996,157(9):3804-3811
[283]Dhalla N S,Elmoselhi A B,Hata T,et al.Status of myocardial antioxidants in ischemia-reperfusion injury[J].Cardiovasc Res,2000,47(3):446-459
[284]Inserte J,Taimor G,Hofstaetter B,et al.Influence of simulated ischemia on apoptosis induction by oxidants stress in adult cardiomyocytes of rat[J].Am J Physiol Heart Circ Physiol,2000,278(1):94-99
[285]Uchida Y,Takio K,Titani K et al.The Growth Inhinitory Factor That Is Deficient in the Alzheimer's Disease Brain Is a 68 Amino Acid Metallothionein-like Protein[J].Neuron,1991,7:337-347
[286]Palmiter R D,Findley S D,Whitmore T E,et al.MT-,a brain-specific member of the metallothionein gene family[J].Proc Natl Acad Sci USA,1992,89:6333-6337
[287]Liu W,Saint D A.A new quantitative method of real-time reverse transcription polymerase chain assay based ob simulation of polymerase chain reaction kinetics[J].Anal Biochem,2002,302(1):52-59.
[288]张弛宇,徐顺高,黄发祥.一种新颖简便的荧光实时定量RT-PCR相对定量方法的建立[J].生物化学与生物物理进展,2005,32(9):883-888
[289]张立国,张琚.实时定量PCR技术的介绍[J].生物技术,2003,13(2):39-40
[290]Kagi J H R,Hunziker P,Vasak M.Metallothionein:Biochemistry and spatial structure[J].Trace elements in clinical medicine,1990:395-403
[291] Vasak M, Hasler D W. Metallothionein: new functional and structural insights [J].Cur Opin Chem Bio, 2000,4:177-183
[292] Yamada M, Hayashi H, Hozumi I, et al. Subcellular location of growth inhibitory factor in rat brain: Light and electron microscopic immunohistochemical studies [J]. Brain Res, 1996, 735: 257-264
[293] Bremner I. Interaction between metallothionein and trace metals [J]. Progr in Food Nutr Sci, 1987, 11: 1-37
[294] Heinrich P C, Castell J V, Andus T. Interleukin-6 and the acute phase response [J]. Biochem J, 1990,265:621-636
[295]Tamai K T, Liu X, Silar P, et al. Heat shock transcription factor activates yeast metalloth- ionein gene expression in response to heat and glucose starvation via distinct siganlling pathways [J]. Mol Cell Biol, 1994, 141(2): 8155-8165
[296] Durnam D M, Palmiter R D. Transcriptional regulation of the mouse metallothionein I gene by heavy metals [J]. J Biol Chem, 1981, 256: 5712-5716
[297] Palmiter R D. Molecular biology of metallothionein in animal tissues [J]. Eisei Kagaku, 1987, 24: 128-131
[298] Holt D, Magos L, Webb M. The interaction of cadmium-induced rat renal metallothionein with bivalent mercury in vitro [J]. Chem Biol Interact, 1980, 32: 125-135
[299] Park J D, Liu Y, Klaassen C D. Protective effect of metallothionein against the toxicity of cadmium and other metals [J]. Toxicology, 2001, 163: 93-100
[300] Gong Q, Hart B A. Effect of thiols on cadmium-induced expression of metallothionein and other oxidant stress genes in rat lung epithelial cells [J]. Toxicology, 1997, 119(3): 179-191
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |