大气细颗粒物对大鼠胸主动脉收缩、舒张功能的影响及与NOS/NO通路的关系
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摘要
研究目的:通过制备大鼠胸主动脉血管环,观察大气细颗粒物(PM_(2.5))水溶成分对大鼠离体胸主动脉血管收缩、舒张有无影响,进一步探讨对内皮细胞的影响机制。
研究方法:Wistar雄性大鼠18只,分离胸主动脉制备内皮完整、去内皮血管环,进行下列研究:1.大气PM_(2.5)水溶成分对正常大鼠胸主动脉收缩功能的影响:观察大气PM_(2.5)(0μg/ml、10μg/ml、100μg/ml )对不同浓度苯肾上腺素(PE)引发内皮完整血管环或去内皮血管环收缩的影响;内皮完整血管环同时以超氧化物歧化酶(SOD)联合二甲基亚砜(DMSO)干预,探讨干预对大气PM_(2.5)水溶成分(100μg/ml)作用有无影响。2.大气PM_(2.5)水溶成分对正常大鼠胸主动脉舒张功能的影响:内皮完整血管环以10-6NE预收缩,观察大气PM_(2.5)(0μg/ml、10μg/ml、100μg/ml )对不同浓度乙酰胆碱(ACH)引起的内皮依赖性舒张作用的影响,同时以SOD联合DMSO干预,探讨干预对大气PM_(2.5)水溶成分(100μg/ml)作用有无影响。
研究结果:1.不同浓度大气PM_(2.5)水溶成分对静息状态的血管环无直接影响。2. PE在10-5mol/L水平,100μg/ml组收缩率(%)为88.04±2.34,高于0μg/ml组(79.10±7.95)、10μg/ml组( 80.83±5.41 )、SOD+DMSO+PM100组( P<0.05或P<0.01 );L-NAME+PM100组收缩率( 96.80±2.21 )高于100μg/ml组( P<0.05 ),SOD+DMSO+PM100组收缩率和0μg/ml组间无显著性差异(P>0.05)。3. ACH在10-5mol/L水平时,PM_(2.5)100μg/ml引起的舒张率(%)为36.80±5.41,小于对照组、PM_(2.5)10μg/ml组(P<0.01),SOD+DMSO+PM_(2.5)100μg/ml组与对照组无差别(P >0.05)。
研究结论:大气PM_(2.5)水溶成分可内皮依赖性地加强PE对血管环的收缩作用,减弱ACH所致的血管舒张作用,其机制可能与其通过氧化应激引起内皮细胞功能障碍有关。
研究目的:探讨大气PM_(2.5)水溶成分静脉染毒后1h、6h,正常大鼠、动脉粥样硬化大鼠胸主动脉血管环在两个时间点收缩、舒张功能有无差别。
研究方法:雄性Wistar大鼠60只,随机分为对照组、对照1h组、对照6h组、动脉硬化组、动脉硬化1h组、动脉硬化6h组,每组10只。染毒组以大气PM_(2.5)水溶成分(1ml/kg)尾静脉注射1h、6h后,分别以25%乌拉坦腹腔注射(0.4ml/100g)麻醉后,迅速开胸取大鼠胸主动脉,制备血管环,置于张力换能器进行实验。
研究结果: 1.动脉粥样硬化大鼠模型成功制备。2.舒张功能比较:(1) ACH舒张: ACH在10-5mol/L水平(10-6mol/LNE预收缩),对照1h组舒张率(47.62±13.19)%与对照组(68.69±6.52)%、对照6h组(65.65±7.09)%相比下降(P<0.01);后两组舒张率无显著性差异( P>0.05);ACH在10-5mol/L水平(60mmol/LKCL预收缩),对照组、对照1h组、对照6h组三组间无显著性差异;ACH在10-5mol/L水平(10-6NE预收缩),与动脉硬化组相比动脉硬化1h组舒张率下降32.63%(P<0.01),动脉硬化6h组与动脉硬化组舒张率无显著性差异;ACH在10-5mol/L水平(60mmol/LKCL预收缩),动脉硬化1h组舒张率降低42.72%(P<0.001),动脉硬化6h组与动脉硬化组无显著性差异( P>0.05)。(2)硝普钠(SNP)舒张:SNP在10-5mol/L水平(10-6mol/LNE预收缩),对照1h组舒张率(77.34±9.60)%与对照组(93.62±3.26)%、对照6h组(82.52±6.16)%相比下降(P<0.01),后两组舒张率无显著性差异( P>0.05);正常组大鼠在60mmol/LKCL预收缩,三组间舒张率无显著性差异( P>0.05),动脉硬化大鼠在10-6mol/LNE、60mmol/LKCL预收缩,三组间也无显著性差异( P>0.05)。3.收缩功能比较:正常大鼠胸主动脉在不同PE浓度水平收缩,三组间收缩率无显著差异( P>0.05)。动脉硬化大鼠,PE在10-5mol/L水平,动脉硬化1h组收缩率为(76.06±19.86)%,高于动脉硬化组(54.13±17.44)%及动脉硬化6h组(44.80±12.64)%(P<0.05),后两组间无显著性差异( P>0.05)。
研究结论:1.大气PM_(2.5)水溶成分静脉染毒正常大鼠、动脉粥样硬化大鼠1h后可引起两组大鼠主动脉舒张减弱、动脉粥样硬化大鼠主动脉收缩增强,6h后该作用减弱。2.大气PM_(2.5)水溶成分对血管的直接损害可能不仅仅限于血管内皮。
研究目的:本研究拟通过大气PM_(2.5)经尾静脉急性染毒正常大鼠、动脉粥样硬化大鼠,以染毒后1h为观察作用点,探讨大气PM_(2.5)对大鼠血管内皮细胞NOS/NO系统表达的影响。
研究方法: 40只健康Wistar雄性大鼠,适应性喂养1周后,随机分为4组,每组10只,分别为:对照组、对照1h组、动脉硬化组、动脉硬化1h组。12周造模成功后开始试验。对照1h组、动脉硬化1h组尾静脉注射大气PM_(2.5)水溶成分(1ml/kg)。尾静脉注射1h后25%乌拉坦腹腔注射(0.4ml/100g)麻醉试验大鼠,迅速行右侧颈动脉插管,同步记录血压波形与心电图波形。待血压波形平稳后截取10min血压波形与心电图波形,计算血压平均值、心率平均值。记录完毕腹主动脉采取动脉血制备血清标本,心脏停跳前迅速开胸暴露心脏,取出主动脉并固定、制备石蜡切片。标本制备好后进行相应指标测定。
研究结果: 1.大气PM_(2.5)对正常大鼠、动脉粥样硬化大鼠血压、心率的影响:(1)正常组染毒后1h,收缩压较对照组增高,(141.12±13.55) mmHg vs (122.24±13.92)mmHg,P<0.05。动脉硬化组染毒后1h,收缩压较动脉硬化组降低,(112.86±20.38) mmHg vs (131.50±13.55)mmHg,P<0.05。(2)正常组染毒后1h,心率较对照组增高,(377.48±41.45)次/min vs (345.69±38.82)次/min,P<0.05。动脉硬化组染毒后1h,心率较动脉硬化组降低,(204.07±23.66)次/min vs( 238.46±32.14)次/min,P<0.05。2.大气PM_(2.5)对正常大鼠、动脉硬化大鼠血清各指标的影响:(1)正常组染毒后1h,血清NO水平较正常组降低, P<0.01;同样动脉硬化组染毒后1h,血清NO水平较动脉硬化组降低, P<0.05。(2)正常组染毒后1h,血清iNOS水平较正常组升高,P<0.01;同样动脉硬化组染毒后1h,血清iNOS水平较动脉硬化组升高,P<0.05。(3)血清eNOS水平各组间比较,无显著性差异,P>0.05。3.大气PM_(2.5)对正常大鼠、动脉硬化大鼠血管内皮、内皮下iNOS、eNOS、Nrf2蛋白表达的影响:(1)正常组染毒后1h,胸主动脉内皮及内皮下eNOS蛋白水平较正常组减少,P<0.05;动脉硬化组染毒后1h,胸主动脉内皮、内皮下eNOS蛋白较动脉硬化组减少, P<0.05。(2)正常组染毒后1h,胸主动脉内皮及内皮下iNOS蛋白水平较正常组增高,P<0.05。动脉硬化组染毒后1h,胸主动脉内皮下iNOS蛋白较动脉硬化组增高, P<0.05。(3)正常组染毒后1h,胸主动脉内皮及内皮下Nrf2蛋白水平较正常组增加,P<0.05。动脉硬化组染毒后1h,胸主动脉内皮下Nrf2蛋白水平较动脉硬化组表达增加,而内皮Nrf2蛋白水平较动脉硬化组无显著性差别,P>0.05。
研究结论: 1.大气PM_(2.5)急性染毒引起正常大鼠、动脉粥样硬化大鼠血压、心率改变,其机制与血管内皮及内皮下管壁NOS/NO系统表达异常有关。2.动脉粥样硬化大鼠内皮细胞NOS/NO表达异常,大气PM_(2.5)进一步加剧了NOS/NO的异常表达,提示大气PM_(2.5)染毒更易引起动脉粥样硬化大鼠发生心血管事件。3.大气PM_(2.5)在引起内皮细胞氧化应激的同时,可能引起内皮细胞抗氧化系统的激活。
Objective: By preparation of endothelium rings of rat thoracic aortas, to observe the effects of WSC of Fine Particulate Materials (PM_(2.5)) on the contraction and relaxation in isolated rat thoracic aortas and to discuss its possible mechanisms to affect endothelial cells.
Methods: Isolated thoracic aortas of 18 Wistar rats were prepared and subjected to the following experiments: 1.the effects of PM_(2.5) on the contraction of thoracic aortas in normal rats: the effects of 0μg/ml、10μg/ml、100μg/ml PM_(2.5) on the contraction of intact endothelium rings and denude endothelium rings induced by Phenylephrine(PE) at different concentrations; intact endothelium rings being pretreated with superoxide dismutase(SOD) combined with Dimethyl sulphoxide (DMSO), to discuss the influence of pretreatment on effects of 100μg/ml PM_(2.5). 2. the effects PM_(2.5) on the relaxation of thoracic aortas in normal rats: intact endothelium rings being pre-contracted with 10-6NE, to observe the effects of 0μg/ml、10μg/ml、100μg/ml PM_(2.5) on the relaxation of denude endothelium rings induced by ACH at different concentrations, and to discuss the influence of pretreatment with superoxide dismutase(SOD) combined with Dimethyl sulphoxide (DMSO) on effects of 100μg/ml PM_(2.5).
Results:1. no direct effect of WSC for PM_(2.5) at different concentrations on endothelium rings in quiescent condition. 2. PE at 10-5mol/L, concentration rate as 88.04±2.34 for 100μg/ml, higher than 0μg/ml (79.10±7.95) or10μg/ml (80.83±5.41)and SOD+DMSO + PM100(P<0.05或P<0.01);concentration rate of L-NAME+PM100 (96.80±2.21) was higher than 100μg/ml (P<0.05),no significant difference for 0μg/ml and SOD+DMSO+ PM100 (P>0.05). 3. Ach at 10-5mol/L, relaxation rate induced by 100μg/ml PM_(2.5) was 36.80±5.41, lower than control. No significant differences were observed among 10μg/ml PM_(2.5) (P<0.01),SOD+DMSO +PM_(2.5)100μg/m and control group (P >0.05).
Conclusions: PM_(2.5) can markedly promote contraction of PE to endothelium rings and weaken relaxation induced by ACH, with probable mechanism related to oxidative impairment in endothelial cells.
Objective: to discuss the difference of concentration and relaxation of thoracic aortas endothelium rings of both normal rats and arteriosclerosis rats, at 1h and 6h after being injected with WSC of PM_(2.5).
Methods: Male Wistar rats being randomly divided into control group, 1h control group, 6h control group, atherosclerosis group, 1h atherosclerosis group, 6h atherosclerosis group, 10 for each group. For exposure group, 1h or 6h after intravenous injection of WSC of PM_(2.5) (1ml/kg), anesthesia with peritoneal injection (0.4ml/100g) of 25% urethan, to prepare endothelium rings with thoracic aortas, put endothelium rings on tonotransducer.
Results: 1.successfully prepare atherosclerosis rats models. 2.Comparation of relaxation (1) ACH relaxation: Compared to control group, 6h control group, Ach at 10-5mol/L (10-6MNE pretreatment), relaxation of 1h control group decreased with significant difference (P<0.001); no significant difference on relaxation rate for control group and 6h control group( P>0.05); Ach at 10-5mol/L (precontracted with 60mmol/LKCL), no significant difference among control group, 1h control group and 6h control group; Ach at 10-5mol/L (precontracted with 10-6MNE), compared to atherosclerosis group, relaxation rate of 1h atherosclerosis rats decreased by 32.63% (P<0.01),no significant difference on relaxation rate for 6h atherosclerosis group and atherosclerosis group; Ach at 10-5mol/L(precontracted with 60mmol/LKCL),relaxation rate of 1h atherosclerosis group decreased by 42.72%(P<0.001), no significant difference for 6h atherosclerosis group and atherosclerosis group( P>0.05). (2)SNP relaxation: SNP at 10-5mol/L(precontracted with 10-6MNE),compared to control group (relaxation rate (93.62±3.26)%) and 6h control group (relaxation rate (82.52±6.16)%), relaxation rate of 1h control group dropped to (77.34±9.60)%(P<0.01); no significant difference on relaxation between later groups ( P>0.05);rats in control group precontracted at 60mmol/LKCL, no significant difference on relaxation rate among three groups( P>0.05),atherosclerosis rats precontracted at 10-6MNE or 60 mmol/LKCL, also no significant difference among three groups(P>0.05). 3.comparation of contractile function: thoracic aortas of rats in control group contracted at different PE concentrations, no significant difference on contraction rate among three groups ( P>0.05); for atherosclerosis rats, PE at 10-5mol/L, contraction rate for 1h group was (76.06±19.86)%, higher than atherosclerosis group (54.13±17.44)% and 6h atherosclerosis group (44.80±12.64)% (P<0.05). No significant difference between later two groups ( P>0.05).
Conclusions: For normal rats and atherosclerosis rats, 1h after intravenous injection with WSC of PM_(2.5), relaxation is weakened. In addition, for atherosclerosis rats 1h after intravenous injection with WSC of PM_(2.5), contraction is enhanced, which will be weakened 6h later. The impairment of WSC of PM_(2.5) to vascular functions is not only limited to vascular endothelium.
Objective: With normal rats and atherosclerosis rats injected by vein in the tail with WSC of PM_(2.5), at the basis of 1h after injection, to discuss the effects of WSC of PM_(2.5) on NOS-NO system in the endothelial cells from rat thoracic aortas
Methods: 40 healthy male Wistar rats, being acclimatized for one week, were divided randomly into 4 groups (10 for each group) as: control group, 1h control group, atherosclerosis group, 1h atherosclerosis group. Experiment was made 12 weeks later. Control group and atherosclerosis group were injected by vein in the tail with saline water (1ml/kg), 1h control group and 1h atherosclerosis group were injected by vein in the tail with WSC of PM_(2.5).. l hour after injection , rats were anesthetized with intraperitoneal injection of urethane(0.4ml/100g), carotid spiled on the right, recording waveform of blood pressure and electrocardiogram. Investigating and recording waveform of blood pressure, intercepting 10min of blood pressure and electrocardiogram when stable, to calculate the average of blood pressure and heart rate. After recording, to prepare serum with arterial blood from abdominal aorta, to expose heart before stop beating, to remove aorta to fix and prepare paraffin section. The relevant indicators should be tested after the preparation of specimen.
Results: 1.Effects of PM_(2.5) on blood pressure and heart rate of normal rats and arteriosclerosis rats. (1) For 1h control group, systolic pressure was higher than control group, (141.12±13.55) mmHg vs (122.24±13.92)mmHg,P<0.05. For 1h arteriosclerosis group, systolic pressure was lower than arteriosclerosis group, (112.86±20.38) mmHg vs (131.50±13.55)mmHg,P<0.05. (2) For 1h control group, heart rate was higher than control group, (377.48±41.45)times/min vs (345.69±38.82) times /min,P<0.05. For 1h arteriosclerosis exposure group, heart rate was lower than arteriosclerosis group, (204.07±23.66)times/min vs( 238.46±32.14) times /min,P<0.05. 2. Effect of PM_(2.5) on each item of blood-serum in normal rats and arteriosclerosis rats. (1) For 1h control group, NO level of blood-serum was lower than control group P<0.01. For 1h arteriosclerosis group, NO level of blood-serum was lower than arteriosclerosis group, P<0.05. (2) For 1h control group, iNOS level of blood-serum was higher than control group P<0.01. For 1h arteriosclerosis group, iNOS level of blood-serum was higher than arteriosclerosis group, P<0.05. (3) No significant difference on eNOS level of blood-serum among several groups P>0.05. 3. Effect of PM_(2.5) on iNOS, eNOS, Nrf2 proteins on endothelium and the wall under endothelium of blood vessel in normal rats and arteriosclerosis rats. (1) For 1h control group, eNOS protein level of aorta was lower than control group P<0.05;for 1h arteriosclerosis group, eNOS protein of aorta was lower than arteriosclerosis group P<0.05. (2) For 1h control group, iNOs protein level of aorta was higher than control group P<0.05. For 1h arteriosclerosis group, iNOs protein level of the wall under endothelium was higher than arteriosclerosis group P<0.05. (3) For 1h control group, Nrf2 protein level of endothelium and the wall under endothelium in aorta was higher than control group, P<0.05. For 1h arteriosclerosis group, Nrf2 protein level of the wall under endothelium in aorta was higher than arteriosclerosis group, but no significant difference on Nrf2 protein level of endothelium with arteriosclerosis group, P>0.05.
Conclusions: Active exposure of WSC of PM_(2.5) induces a change of blood pressure and heart rate in both normal rats and atherosclerosis rats, which is related to oxidative stress in mechanism. The disorder of NOS/NO is one of the mechanisms of impairment of PM_(2.5) on endothelial cells. PM_(2.5) further strengthens the disorder of NOS/NO of endothelial cells in atherosclerosis rats. PM_(2.5) induces the activation of antioxidation system in endothelial cells.
研究方法:Wistar雄性大鼠18只,分离胸主动脉制备内皮完整、去内皮血管环,进行下列研究:1.大气PM_(2.5)水溶成分对正常大鼠胸主动脉收缩功能的影响:观察大气PM_(2.5)(0μg/ml、10μg/ml、100μg/ml )对不同浓度苯肾上腺素(PE)引发内皮完整血管环或去内皮血管环收缩的影响;内皮完整血管环同时以超氧化物歧化酶(SOD)联合二甲基亚砜(DMSO)干预,探讨干预对大气PM_(2.5)水溶成分(100μg/ml)作用有无影响。2.大气PM_(2.5)水溶成分对正常大鼠胸主动脉舒张功能的影响:内皮完整血管环以10-6NE预收缩,观察大气PM_(2.5)(0μg/ml、10μg/ml、100μg/ml )对不同浓度乙酰胆碱(ACH)引起的内皮依赖性舒张作用的影响,同时以SOD联合DMSO干预,探讨干预对大气PM_(2.5)水溶成分(100μg/ml)作用有无影响。
研究结果:1.不同浓度大气PM_(2.5)水溶成分对静息状态的血管环无直接影响。2. PE在10-5mol/L水平,100μg/ml组收缩率(%)为88.04±2.34,高于0μg/ml组(79.10±7.95)、10μg/ml组( 80.83±5.41 )、SOD+DMSO+PM100组( P<0.05或P<0.01 );L-NAME+PM100组收缩率( 96.80±2.21 )高于100μg/ml组( P<0.05 ),SOD+DMSO+PM100组收缩率和0μg/ml组间无显著性差异(P>0.05)。3. ACH在10-5mol/L水平时,PM_(2.5)100μg/ml引起的舒张率(%)为36.80±5.41,小于对照组、PM_(2.5)10μg/ml组(P<0.01),SOD+DMSO+PM_(2.5)100μg/ml组与对照组无差别(P >0.05)。
研究结论:大气PM_(2.5)水溶成分可内皮依赖性地加强PE对血管环的收缩作用,减弱ACH所致的血管舒张作用,其机制可能与其通过氧化应激引起内皮细胞功能障碍有关。
研究目的:探讨大气PM_(2.5)水溶成分静脉染毒后1h、6h,正常大鼠、动脉粥样硬化大鼠胸主动脉血管环在两个时间点收缩、舒张功能有无差别。
研究方法:雄性Wistar大鼠60只,随机分为对照组、对照1h组、对照6h组、动脉硬化组、动脉硬化1h组、动脉硬化6h组,每组10只。染毒组以大气PM_(2.5)水溶成分(1ml/kg)尾静脉注射1h、6h后,分别以25%乌拉坦腹腔注射(0.4ml/100g)麻醉后,迅速开胸取大鼠胸主动脉,制备血管环,置于张力换能器进行实验。
研究结果: 1.动脉粥样硬化大鼠模型成功制备。2.舒张功能比较:(1) ACH舒张: ACH在10-5mol/L水平(10-6mol/LNE预收缩),对照1h组舒张率(47.62±13.19)%与对照组(68.69±6.52)%、对照6h组(65.65±7.09)%相比下降(P<0.01);后两组舒张率无显著性差异( P>0.05);ACH在10-5mol/L水平(60mmol/LKCL预收缩),对照组、对照1h组、对照6h组三组间无显著性差异;ACH在10-5mol/L水平(10-6NE预收缩),与动脉硬化组相比动脉硬化1h组舒张率下降32.63%(P<0.01),动脉硬化6h组与动脉硬化组舒张率无显著性差异;ACH在10-5mol/L水平(60mmol/LKCL预收缩),动脉硬化1h组舒张率降低42.72%(P<0.001),动脉硬化6h组与动脉硬化组无显著性差异( P>0.05)。(2)硝普钠(SNP)舒张:SNP在10-5mol/L水平(10-6mol/LNE预收缩),对照1h组舒张率(77.34±9.60)%与对照组(93.62±3.26)%、对照6h组(82.52±6.16)%相比下降(P<0.01),后两组舒张率无显著性差异( P>0.05);正常组大鼠在60mmol/LKCL预收缩,三组间舒张率无显著性差异( P>0.05),动脉硬化大鼠在10-6mol/LNE、60mmol/LKCL预收缩,三组间也无显著性差异( P>0.05)。3.收缩功能比较:正常大鼠胸主动脉在不同PE浓度水平收缩,三组间收缩率无显著差异( P>0.05)。动脉硬化大鼠,PE在10-5mol/L水平,动脉硬化1h组收缩率为(76.06±19.86)%,高于动脉硬化组(54.13±17.44)%及动脉硬化6h组(44.80±12.64)%(P<0.05),后两组间无显著性差异( P>0.05)。
研究结论:1.大气PM_(2.5)水溶成分静脉染毒正常大鼠、动脉粥样硬化大鼠1h后可引起两组大鼠主动脉舒张减弱、动脉粥样硬化大鼠主动脉收缩增强,6h后该作用减弱。2.大气PM_(2.5)水溶成分对血管的直接损害可能不仅仅限于血管内皮。
研究目的:本研究拟通过大气PM_(2.5)经尾静脉急性染毒正常大鼠、动脉粥样硬化大鼠,以染毒后1h为观察作用点,探讨大气PM_(2.5)对大鼠血管内皮细胞NOS/NO系统表达的影响。
研究方法: 40只健康Wistar雄性大鼠,适应性喂养1周后,随机分为4组,每组10只,分别为:对照组、对照1h组、动脉硬化组、动脉硬化1h组。12周造模成功后开始试验。对照1h组、动脉硬化1h组尾静脉注射大气PM_(2.5)水溶成分(1ml/kg)。尾静脉注射1h后25%乌拉坦腹腔注射(0.4ml/100g)麻醉试验大鼠,迅速行右侧颈动脉插管,同步记录血压波形与心电图波形。待血压波形平稳后截取10min血压波形与心电图波形,计算血压平均值、心率平均值。记录完毕腹主动脉采取动脉血制备血清标本,心脏停跳前迅速开胸暴露心脏,取出主动脉并固定、制备石蜡切片。标本制备好后进行相应指标测定。
研究结果: 1.大气PM_(2.5)对正常大鼠、动脉粥样硬化大鼠血压、心率的影响:(1)正常组染毒后1h,收缩压较对照组增高,(141.12±13.55) mmHg vs (122.24±13.92)mmHg,P<0.05。动脉硬化组染毒后1h,收缩压较动脉硬化组降低,(112.86±20.38) mmHg vs (131.50±13.55)mmHg,P<0.05。(2)正常组染毒后1h,心率较对照组增高,(377.48±41.45)次/min vs (345.69±38.82)次/min,P<0.05。动脉硬化组染毒后1h,心率较动脉硬化组降低,(204.07±23.66)次/min vs( 238.46±32.14)次/min,P<0.05。2.大气PM_(2.5)对正常大鼠、动脉硬化大鼠血清各指标的影响:(1)正常组染毒后1h,血清NO水平较正常组降低, P<0.01;同样动脉硬化组染毒后1h,血清NO水平较动脉硬化组降低, P<0.05。(2)正常组染毒后1h,血清iNOS水平较正常组升高,P<0.01;同样动脉硬化组染毒后1h,血清iNOS水平较动脉硬化组升高,P<0.05。(3)血清eNOS水平各组间比较,无显著性差异,P>0.05。3.大气PM_(2.5)对正常大鼠、动脉硬化大鼠血管内皮、内皮下iNOS、eNOS、Nrf2蛋白表达的影响:(1)正常组染毒后1h,胸主动脉内皮及内皮下eNOS蛋白水平较正常组减少,P<0.05;动脉硬化组染毒后1h,胸主动脉内皮、内皮下eNOS蛋白较动脉硬化组减少, P<0.05。(2)正常组染毒后1h,胸主动脉内皮及内皮下iNOS蛋白水平较正常组增高,P<0.05。动脉硬化组染毒后1h,胸主动脉内皮下iNOS蛋白较动脉硬化组增高, P<0.05。(3)正常组染毒后1h,胸主动脉内皮及内皮下Nrf2蛋白水平较正常组增加,P<0.05。动脉硬化组染毒后1h,胸主动脉内皮下Nrf2蛋白水平较动脉硬化组表达增加,而内皮Nrf2蛋白水平较动脉硬化组无显著性差别,P>0.05。
研究结论: 1.大气PM_(2.5)急性染毒引起正常大鼠、动脉粥样硬化大鼠血压、心率改变,其机制与血管内皮及内皮下管壁NOS/NO系统表达异常有关。2.动脉粥样硬化大鼠内皮细胞NOS/NO表达异常,大气PM_(2.5)进一步加剧了NOS/NO的异常表达,提示大气PM_(2.5)染毒更易引起动脉粥样硬化大鼠发生心血管事件。3.大气PM_(2.5)在引起内皮细胞氧化应激的同时,可能引起内皮细胞抗氧化系统的激活。
Objective: By preparation of endothelium rings of rat thoracic aortas, to observe the effects of WSC of Fine Particulate Materials (PM_(2.5)) on the contraction and relaxation in isolated rat thoracic aortas and to discuss its possible mechanisms to affect endothelial cells.
Methods: Isolated thoracic aortas of 18 Wistar rats were prepared and subjected to the following experiments: 1.the effects of PM_(2.5) on the contraction of thoracic aortas in normal rats: the effects of 0μg/ml、10μg/ml、100μg/ml PM_(2.5) on the contraction of intact endothelium rings and denude endothelium rings induced by Phenylephrine(PE) at different concentrations; intact endothelium rings being pretreated with superoxide dismutase(SOD) combined with Dimethyl sulphoxide (DMSO), to discuss the influence of pretreatment on effects of 100μg/ml PM_(2.5). 2. the effects PM_(2.5) on the relaxation of thoracic aortas in normal rats: intact endothelium rings being pre-contracted with 10-6NE, to observe the effects of 0μg/ml、10μg/ml、100μg/ml PM_(2.5) on the relaxation of denude endothelium rings induced by ACH at different concentrations, and to discuss the influence of pretreatment with superoxide dismutase(SOD) combined with Dimethyl sulphoxide (DMSO) on effects of 100μg/ml PM_(2.5).
Results:1. no direct effect of WSC for PM_(2.5) at different concentrations on endothelium rings in quiescent condition. 2. PE at 10-5mol/L, concentration rate as 88.04±2.34 for 100μg/ml, higher than 0μg/ml (79.10±7.95) or10μg/ml (80.83±5.41)and SOD+DMSO + PM100(P<0.05或P<0.01);concentration rate of L-NAME+PM100 (96.80±2.21) was higher than 100μg/ml (P<0.05),no significant difference for 0μg/ml and SOD+DMSO+ PM100 (P>0.05). 3. Ach at 10-5mol/L, relaxation rate induced by 100μg/ml PM_(2.5) was 36.80±5.41, lower than control. No significant differences were observed among 10μg/ml PM_(2.5) (P<0.01),SOD+DMSO +PM_(2.5)100μg/m and control group (P >0.05).
Conclusions: PM_(2.5) can markedly promote contraction of PE to endothelium rings and weaken relaxation induced by ACH, with probable mechanism related to oxidative impairment in endothelial cells.
Objective: to discuss the difference of concentration and relaxation of thoracic aortas endothelium rings of both normal rats and arteriosclerosis rats, at 1h and 6h after being injected with WSC of PM_(2.5).
Methods: Male Wistar rats being randomly divided into control group, 1h control group, 6h control group, atherosclerosis group, 1h atherosclerosis group, 6h atherosclerosis group, 10 for each group. For exposure group, 1h or 6h after intravenous injection of WSC of PM_(2.5) (1ml/kg), anesthesia with peritoneal injection (0.4ml/100g) of 25% urethan, to prepare endothelium rings with thoracic aortas, put endothelium rings on tonotransducer.
Results: 1.successfully prepare atherosclerosis rats models. 2.Comparation of relaxation (1) ACH relaxation: Compared to control group, 6h control group, Ach at 10-5mol/L (10-6MNE pretreatment), relaxation of 1h control group decreased with significant difference (P<0.001); no significant difference on relaxation rate for control group and 6h control group( P>0.05); Ach at 10-5mol/L (precontracted with 60mmol/LKCL), no significant difference among control group, 1h control group and 6h control group; Ach at 10-5mol/L (precontracted with 10-6MNE), compared to atherosclerosis group, relaxation rate of 1h atherosclerosis rats decreased by 32.63% (P<0.01),no significant difference on relaxation rate for 6h atherosclerosis group and atherosclerosis group; Ach at 10-5mol/L(precontracted with 60mmol/LKCL),relaxation rate of 1h atherosclerosis group decreased by 42.72%(P<0.001), no significant difference for 6h atherosclerosis group and atherosclerosis group( P>0.05). (2)SNP relaxation: SNP at 10-5mol/L(precontracted with 10-6MNE),compared to control group (relaxation rate (93.62±3.26)%) and 6h control group (relaxation rate (82.52±6.16)%), relaxation rate of 1h control group dropped to (77.34±9.60)%(P<0.01); no significant difference on relaxation between later groups ( P>0.05);rats in control group precontracted at 60mmol/LKCL, no significant difference on relaxation rate among three groups( P>0.05),atherosclerosis rats precontracted at 10-6MNE or 60 mmol/LKCL, also no significant difference among three groups(P>0.05). 3.comparation of contractile function: thoracic aortas of rats in control group contracted at different PE concentrations, no significant difference on contraction rate among three groups ( P>0.05); for atherosclerosis rats, PE at 10-5mol/L, contraction rate for 1h group was (76.06±19.86)%, higher than atherosclerosis group (54.13±17.44)% and 6h atherosclerosis group (44.80±12.64)% (P<0.05). No significant difference between later two groups ( P>0.05).
Conclusions: For normal rats and atherosclerosis rats, 1h after intravenous injection with WSC of PM_(2.5), relaxation is weakened. In addition, for atherosclerosis rats 1h after intravenous injection with WSC of PM_(2.5), contraction is enhanced, which will be weakened 6h later. The impairment of WSC of PM_(2.5) to vascular functions is not only limited to vascular endothelium.
Objective: With normal rats and atherosclerosis rats injected by vein in the tail with WSC of PM_(2.5), at the basis of 1h after injection, to discuss the effects of WSC of PM_(2.5) on NOS-NO system in the endothelial cells from rat thoracic aortas
Methods: 40 healthy male Wistar rats, being acclimatized for one week, were divided randomly into 4 groups (10 for each group) as: control group, 1h control group, atherosclerosis group, 1h atherosclerosis group. Experiment was made 12 weeks later. Control group and atherosclerosis group were injected by vein in the tail with saline water (1ml/kg), 1h control group and 1h atherosclerosis group were injected by vein in the tail with WSC of PM_(2.5).. l hour after injection , rats were anesthetized with intraperitoneal injection of urethane(0.4ml/100g), carotid spiled on the right, recording waveform of blood pressure and electrocardiogram. Investigating and recording waveform of blood pressure, intercepting 10min of blood pressure and electrocardiogram when stable, to calculate the average of blood pressure and heart rate. After recording, to prepare serum with arterial blood from abdominal aorta, to expose heart before stop beating, to remove aorta to fix and prepare paraffin section. The relevant indicators should be tested after the preparation of specimen.
Results: 1.Effects of PM_(2.5) on blood pressure and heart rate of normal rats and arteriosclerosis rats. (1) For 1h control group, systolic pressure was higher than control group, (141.12±13.55) mmHg vs (122.24±13.92)mmHg,P<0.05. For 1h arteriosclerosis group, systolic pressure was lower than arteriosclerosis group, (112.86±20.38) mmHg vs (131.50±13.55)mmHg,P<0.05. (2) For 1h control group, heart rate was higher than control group, (377.48±41.45)times/min vs (345.69±38.82) times /min,P<0.05. For 1h arteriosclerosis exposure group, heart rate was lower than arteriosclerosis group, (204.07±23.66)times/min vs( 238.46±32.14) times /min,P<0.05. 2. Effect of PM_(2.5) on each item of blood-serum in normal rats and arteriosclerosis rats. (1) For 1h control group, NO level of blood-serum was lower than control group P<0.01. For 1h arteriosclerosis group, NO level of blood-serum was lower than arteriosclerosis group, P<0.05. (2) For 1h control group, iNOS level of blood-serum was higher than control group P<0.01. For 1h arteriosclerosis group, iNOS level of blood-serum was higher than arteriosclerosis group, P<0.05. (3) No significant difference on eNOS level of blood-serum among several groups P>0.05. 3. Effect of PM_(2.5) on iNOS, eNOS, Nrf2 proteins on endothelium and the wall under endothelium of blood vessel in normal rats and arteriosclerosis rats. (1) For 1h control group, eNOS protein level of aorta was lower than control group P<0.05;for 1h arteriosclerosis group, eNOS protein of aorta was lower than arteriosclerosis group P<0.05. (2) For 1h control group, iNOs protein level of aorta was higher than control group P<0.05. For 1h arteriosclerosis group, iNOs protein level of the wall under endothelium was higher than arteriosclerosis group P<0.05. (3) For 1h control group, Nrf2 protein level of endothelium and the wall under endothelium in aorta was higher than control group, P<0.05. For 1h arteriosclerosis group, Nrf2 protein level of the wall under endothelium in aorta was higher than arteriosclerosis group, but no significant difference on Nrf2 protein level of endothelium with arteriosclerosis group, P>0.05.
Conclusions: Active exposure of WSC of PM_(2.5) induces a change of blood pressure and heart rate in both normal rats and atherosclerosis rats, which is related to oxidative stress in mechanism. The disorder of NOS/NO is one of the mechanisms of impairment of PM_(2.5) on endothelial cells. PM_(2.5) further strengthens the disorder of NOS/NO of endothelial cells in atherosclerosis rats. PM_(2.5) induces the activation of antioxidation system in endothelial cells.
引文
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