高渗氯化钠羟乙基淀粉40对大鼠脑缺血再灌注损伤的保护作用
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摘要
研究背景
脑血管疾病是目前危害人类健康的三大疾病之一,在危重患者的抢救过程中,常采取心肺脑复苏、强心利尿、大量输血输液等治疗措施,而处理后容易引起脑缺血再灌注损伤等。近年来国内外对脑缺血再灌注损伤的研究已取得一定成果,但仍缺乏有效的防治措施。因此,探讨有效的防治药物和方法具有重要的理论意义和实践价值。
研究发现高渗氯化钠羟乙基淀粉40(HH40)在神经外科手术中具有减轻脑水肿,降低颅内压(ICP)等脑保护作用。目前国内外对其药理作用的研究较少,因此对于其脑组织缺血再灌注损伤是否具有保护作用有待进一步研究。
目的
本研究旨在观察HH40对大鼠脑缺血再灌注损伤的保护作用并探讨其相关机制,为HH40防治脑缺血再灌注损伤提供实验依据。
方法
72只雄性SD大鼠随机分为假手术组(A组)、模型组(B组)、HH40 4ml/kg组(C组)、HH40 8ml/kg组(D组)。采用大脑中动脉线栓法(MCAO)制备大鼠局灶性脑缺血再灌注损伤模型。制模成功后50min,C、D组舌下静脉输注HH40。再灌注24h后,Longa氏法行神经功能行为学评分;TTC染色法测定脑梗死范围;计算脑组织含水率;比色法测定血清SOD活性、MDA水平;分光光度法检测缺血区脑组织NO含量、iNOS、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase活性的影响;此外用Western Blotting方法检测热休克蛋白70(HSP70)、神经元特异性烯醇化酶(NSE)的表达。
结果与B组比较,C、D组脑梗死体积、缺血侧脑组织含水率、神经功能行为学
评分、血清MDA水平、缺血区脑组织NO含量均降低(p<0.01);C组血清SOD活性升高(p<0.05);C组缺血区脑组织GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase活性升高、iNOS活性低(p<0.01);D组iNOS活性降低(p<0.05)。Western Blotting检测显示:与A组相比,B组NSE、HSP70蛋白表达升高(p<0.01);与B组相比,C组HSP70蛋白表达升高(p<0.05),C、D组NSE表达降低,差异有统计学意义(p<0.01)。
结论
1. HH40可明显缩小大鼠缺血再灌注后脑梗死体积,改善神经功能行为学评分,降低脑组织含水率,提示HH40对脑缺血再灌注损伤有明显的保护作用。
2. HH40可显著降低大鼠缺血再灌注后MDA的生成,降低脑组织NO含量、iNOS活性,提高SOD、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase的活性。表明HH40对脑缺血再灌注损伤的保护作用可能与HH40抗氧化作用、参与NO的调控、抑制iNOS表达及改善脑能量代谢障碍有关。
3. Western Blotting检测显示HH40能上调大鼠缺血再灌注后脑组织HSP70蛋白的表达、降低NSE的表达,提示HH40通过提高HSP70蛋白的表达、降低NSE的表达发挥其保护作用。
Western Blotting检测显示:与A组相比,B组NSE、HSP70蛋白表达升高(p<0.01);与B组相比,C组HSP70蛋白表达升高(p<0.05),C、D组NSE表达降低,差异有统计学意义(p<0.01)。
结论
1. HH40可明显缩小大鼠缺血再灌注后脑梗死体积,改善神经功能行为学评分,降低脑组织含水率,提示HH40对脑缺血再灌注损伤有明显的保护作用。
2. HH40可显著降低大鼠缺血再灌注后MDA的生成,降低脑组织NO含量、iNOS活性,提高SOD、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase的活性。表明HH40对脑缺血再灌注损伤的保护作用可能与HH40抗氧化作用、参与NO的调控、抑制iNOS表达及改善脑能量代谢障碍有关。
3. Western Blotting检测显示HH40能上调大鼠缺血再灌注后脑组织HSP70蛋白的表达、降低NSE的表达,提示HH40通过提高HSP70蛋白的表达、降低NSE的表达发挥其保护作用。
Results
Compared with group B, the volume of infarction and neurological behavioral score were both reduced in group C and D(p<0.01). In addition, water content of left brain and the level of MDA in serum and NO contents of ischemic brain tissue were also reduced in group C and D(p<0.01),while SOD activity was increased and water content of right brain was reduced in group C(p<0.05). GSH-Px, Na~+-K~+-ATPase and Ca2 +-Mg2 +-ATPase activities were all increased in ischemic brain tissue(p<0.01),while iNOS activity was decreased in group C(p<0.01)and D(p<0.05). Western blotting analysis showed that the expression of HSP70 protein and NSE were increased in group B compared with A(p<0.01); and the expression of NSE protein were declined in group C and D compared with group B(p<0.01); while the expression of HSP70 protein was increased markedly(p<0.01).
Conclusions
1. HH40 could significantly reduce the volume of cerebral infarction, improve neurological behavioral score and decrease water content of injured cerebral tissue, which shows that HH40 has a protective effect on cerebral I/R in vivo.
2. After I/R, the MDA formation in rat was significantly reduced, while SOD, GSH-Px, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities were significantly increased by HH40 infusion, which indicates that the protective effect of HH40 on cerebral I/R may be related to its antioxidant effects, regulating NO levels, inhibiting iNOS activity and improving cerebral energy metabolism.
3. Western blotting analysis showed that HH40 could increase the expression of HSP70 protein and decrease the NSE expression, which suggests that the mechanism of HH40 may be related to the increase of HSP70 expression and the decrease of NSE .
脑血管疾病是目前危害人类健康的三大疾病之一,在危重患者的抢救过程中,常采取心肺脑复苏、强心利尿、大量输血输液等治疗措施,而处理后容易引起脑缺血再灌注损伤等。近年来国内外对脑缺血再灌注损伤的研究已取得一定成果,但仍缺乏有效的防治措施。因此,探讨有效的防治药物和方法具有重要的理论意义和实践价值。
研究发现高渗氯化钠羟乙基淀粉40(HH40)在神经外科手术中具有减轻脑水肿,降低颅内压(ICP)等脑保护作用。目前国内外对其药理作用的研究较少,因此对于其脑组织缺血再灌注损伤是否具有保护作用有待进一步研究。
目的
本研究旨在观察HH40对大鼠脑缺血再灌注损伤的保护作用并探讨其相关机制,为HH40防治脑缺血再灌注损伤提供实验依据。
方法
72只雄性SD大鼠随机分为假手术组(A组)、模型组(B组)、HH40 4ml/kg组(C组)、HH40 8ml/kg组(D组)。采用大脑中动脉线栓法(MCAO)制备大鼠局灶性脑缺血再灌注损伤模型。制模成功后50min,C、D组舌下静脉输注HH40。再灌注24h后,Longa氏法行神经功能行为学评分;TTC染色法测定脑梗死范围;计算脑组织含水率;比色法测定血清SOD活性、MDA水平;分光光度法检测缺血区脑组织NO含量、iNOS、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase活性的影响;此外用Western Blotting方法检测热休克蛋白70(HSP70)、神经元特异性烯醇化酶(NSE)的表达。
结果与B组比较,C、D组脑梗死体积、缺血侧脑组织含水率、神经功能行为学
评分、血清MDA水平、缺血区脑组织NO含量均降低(p<0.01);C组血清SOD活性升高(p<0.05);C组缺血区脑组织GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase活性升高、iNOS活性低(p<0.01);D组iNOS活性降低(p<0.05)。Western Blotting检测显示:与A组相比,B组NSE、HSP70蛋白表达升高(p<0.01);与B组相比,C组HSP70蛋白表达升高(p<0.05),C、D组NSE表达降低,差异有统计学意义(p<0.01)。
结论
1. HH40可明显缩小大鼠缺血再灌注后脑梗死体积,改善神经功能行为学评分,降低脑组织含水率,提示HH40对脑缺血再灌注损伤有明显的保护作用。
2. HH40可显著降低大鼠缺血再灌注后MDA的生成,降低脑组织NO含量、iNOS活性,提高SOD、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase的活性。表明HH40对脑缺血再灌注损伤的保护作用可能与HH40抗氧化作用、参与NO的调控、抑制iNOS表达及改善脑能量代谢障碍有关。
3. Western Blotting检测显示HH40能上调大鼠缺血再灌注后脑组织HSP70蛋白的表达、降低NSE的表达,提示HH40通过提高HSP70蛋白的表达、降低NSE的表达发挥其保护作用。
Western Blotting检测显示:与A组相比,B组NSE、HSP70蛋白表达升高(p<0.01);与B组相比,C组HSP70蛋白表达升高(p<0.05),C、D组NSE表达降低,差异有统计学意义(p<0.01)。
结论
1. HH40可明显缩小大鼠缺血再灌注后脑梗死体积,改善神经功能行为学评分,降低脑组织含水率,提示HH40对脑缺血再灌注损伤有明显的保护作用。
2. HH40可显著降低大鼠缺血再灌注后MDA的生成,降低脑组织NO含量、iNOS活性,提高SOD、GSH-Px、Na~+-K~+-ATPase和Ca~(2+)-Mg~(2+)-ATPase的活性。表明HH40对脑缺血再灌注损伤的保护作用可能与HH40抗氧化作用、参与NO的调控、抑制iNOS表达及改善脑能量代谢障碍有关。
3. Western Blotting检测显示HH40能上调大鼠缺血再灌注后脑组织HSP70蛋白的表达、降低NSE的表达,提示HH40通过提高HSP70蛋白的表达、降低NSE的表达发挥其保护作用。
Results
Compared with group B, the volume of infarction and neurological behavioral score were both reduced in group C and D(p<0.01). In addition, water content of left brain and the level of MDA in serum and NO contents of ischemic brain tissue were also reduced in group C and D(p<0.01),while SOD activity was increased and water content of right brain was reduced in group C(p<0.05). GSH-Px, Na~+-K~+-ATPase and Ca2 +-Mg2 +-ATPase activities were all increased in ischemic brain tissue(p<0.01),while iNOS activity was decreased in group C(p<0.01)and D(p<0.05). Western blotting analysis showed that the expression of HSP70 protein and NSE were increased in group B compared with A(p<0.01); and the expression of NSE protein were declined in group C and D compared with group B(p<0.01); while the expression of HSP70 protein was increased markedly(p<0.01).
Conclusions
1. HH40 could significantly reduce the volume of cerebral infarction, improve neurological behavioral score and decrease water content of injured cerebral tissue, which shows that HH40 has a protective effect on cerebral I/R in vivo.
2. After I/R, the MDA formation in rat was significantly reduced, while SOD, GSH-Px, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities were significantly increased by HH40 infusion, which indicates that the protective effect of HH40 on cerebral I/R may be related to its antioxidant effects, regulating NO levels, inhibiting iNOS activity and improving cerebral energy metabolism.
3. Western blotting analysis showed that HH40 could increase the expression of HSP70 protein and decrease the NSE expression, which suggests that the mechanism of HH40 may be related to the increase of HSP70 expression and the decrease of NSE .
引文
[1] Formisano L, Noh KM, Miyawaki T, et a1.Ischemic insults promote epigenetic reprogramming of mu opioid receptor expression in hippocampal neurons [J].Proc Natl Acad Sci USA, 2007, 104(10): 4170-5.
[2]肖华平,古妙宁,肖金仿,等.高渗盐复合液治疗急性颅内高压伴失血性休克犬的实验研究[J].广东医学,2008,3(29):392-94.
[3]肖诗铭,满晓波,邱秀华,等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠肠缺血-再灌注损伤中L-选择素的表达和中性粒细胞浸润的影响[J].中国医药导刊,2005,7(6):451-53.
[4] Longa E Z, Weinstein P R, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats [J].Stroke, 1989, 20 (1):84-91.
[5]廖维靖,刘淑红,范明线,等.线栓阻断大鼠大脑中动脉制作缺血性脑损伤模型的改良[J].中华物理医学与康复杂志,2002,24(6):6345-6348.
[6]尚进林,孙莉,梁浩等.过氧化物酶体增殖物激活受体1激动剂对小鼠局灶性脑缺血再灌注损伤的保护作用[J].中华神经科杂志,2009,42(3):190-194.
[7]邹景霞,李巧霞,陈学忠,等.脑缺血再灌注损伤的中医药防治进展[J].甘肃中医,2009,22(1):74-75.
[8] Bourekas EC, Slivka AP, Shah R, et a1.Intraarterial thrombolyic therapy with 3 hours of the onset of stroke [J].Neurosurgery, 2004, 54(1): 39-44.
[9] Dhandapani KM,Brann D W.Transforming growth factor-beta:a neuroprotecfive factor in cerebral isehemia [J].Cell Biochem Biophys, 2003,39(1): 13-22.
[10]李建生,马玉羡,郭剑峰.中医药防治脑缺血再灌注损伤的研究进展[J].河南中医药学刊,1999,14(2):6l一64.
[11] Toung T J, Chen C H, Lin C, et al. Osmothertapy with hypertonic saline attenuates water content in brain and extracerebral organs[J].Crit Care Med, 2007, 35(2):526-31.
[12]陈世文,周晓平.高渗盐溶液对脑外伤及合并休克的治疗作用[J].国外医学神经病学神经外科学分册,2004,31(3):241-244 .
[13] Ogden AT, Mayer SA, Connolly ES, et al.Hyperosmolar agent in neurosurgical practive the evolving role of hypertonic saline[J].Neurosurgery 2005, 57(2):207-215.
[14]李良东,黄志华,曾靖,等.DSS对脑缺血再灌注损伤的保护与抗氧化作用的关系[J].中风与神经疾病杂志,2009,(4):407-409.
[15]李良东,黄志华,黎晓,等.PBNA-413对脑缺血再灌注损伤时脑水肿及炎性细胞因子的影响[J].中药药理与临床,2009,23(1):30-31.
[16] Liu T, Clark R K, McDonnell PC, et al. Tumor necrosis factor-alpha expression in ischemic neurons[J]. Stroke, 1994,25(7):1481-8.
[17] Dempsey RJ, Baskaya MK, Dogan A. Attenuation of brain edema, blood-brain barrierbreakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate recepter antagonist, after experimental traumatic brain injury in rats[J]. Neurosurgery, 2000,47 (2):399～406.
[18]郑跃英,兰允平,祝胜美.大鼠脑缺血/再灌注损伤后梗死灶周围水通道蛋白4与血脑屏障通透性的动态变化[J].中国病理生理杂志,2008,24(8):1647-1649、1655.
[19] James HE. The effect of intravenous fluid replacement on the response to mannitol in experimental cerebral edema: an analysis of intracranial pressure, serum osmolality, serum electrolytes, and brain water content[J]. Acta Neurochir Suppl, 2006, 96: 125 - 9.
[20] Jones NC, Constantin D, Prior MJ, et al . The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression [J]. Eur J Neurosci, 2005, 21 (6): 1547 - 54.
[21]薛晶,韩冬,邓方,等.拉奉对脑缺血再灌注损伤保护作用机制的研究[J].中风与神经疾病杂志,2009,26(1)18-20.
[22] Saito A, Maier C M, Narasimhan P, et a1.Oxidative stress and neuronal death/survival signaling in cerebralischemia[J].Mol Neurobiol,2005,31(1-3):105-16.
[23] Yamawaki M, Sasaki N, Shimoyama M, et a1.Protective effect of edaravone against hypoxia—reoxygenation injury in rabbit cardiomyocytes [J].Br J Pharmacol,2004,142(3):618-26.
[24]吕平,郭芳,张目红,等.双苯氟嗪对脑缺血再灌注损伤后脑组织及血清中NO、NOS、iNOS的影响[J].中国药理学通报,2005,21(11):1340—1343.
[25]吕鸿燕,朱旭友,陈前芬.硫酸镁预处理对小鼠全脑缺血再灌注损伤后一氧化氮及一氧化氮合酶的影响[J].蚌埠医学院学报,2009,34(9)762-764.
[26] Tsai SK, Hung LM, Fu YT, et a1.Resveratrol neuroproteetive effects during focal cerebral ischemia injury via nitric oxide mechanism in rats[J].J Vase Surg,2007,46(2):346-53.
[27] xu J, He L, Ahmed SH, et al.Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells [J].Stroke,2000,31(7):1744—51.
[28]苗明山,张桂兰,张玉林.醒脑再造胶囊对大鼠血瘀性脑缺血模型脑组织的影响[J].中药药理与临床,2007,23(3):69-70.
[29]宋翠荣,杨艳梅,刘建辉,等.新生儿缺血缺氧性脑病生物学指标的研究进展[J].中外健康文摘,2009,6(11)237-238.
[30]贺勇,尤志瑶,周少华,等.短暂性脑缺血发作患者血清S- 100和神经元特异性烯醇化酶的测定及临床意义[J].实用医学杂志,2005,21(1):37-38.
[31] Abraha HD, Butterworth RJ, Bath PM, et al.Serum S-100 protein , relationship to clinical outcome in acute stroke [J].Ann Clin Biochem, 1997, 34(4):366-70.
[32] Wang S, Xu X, Gu L. Changes in the expression of C-fos & heat shock protein genes & blood flow velocity in the brain of rats undergoing myocardial ischaemia /reperfusion[J].Indian J Med Res, 2006, 123(2):131-38.
[33] Franklin TB, Krueger-Nang AM, Clarke DB, et a1.The role of heat shock proteins Hsp70 andHsp27 in cellular protection of the central nervous system[J].Int J Hyperthermia, 2005, 21(5):379- 92.
[34] Lee SH, Kwon H M, Kim Y J, et al. Effects of hsp70.l gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia [J]. Stroke, 2004,35(9):2195-9.
[1] Boldt J, Fluid choice for resuscitation of the trauma patient: a review of the physiological, pharmacological and clinical evidence [J]. Can J Anesth, 2004,51(5):500-513.
[2] Ogden A T, Mayer S A, Connolly E S, et al.Hyperosmolar agent in neurosurgical practice: the evolving role of hypertonic saline [J]. Neurosurgery, 2005, 57(2): 207-15.
[3] Toung T J, Chen C H, Lin C, et al.Osmothertapy with hypertonic saline attenuates water content in brain and extracerebral organs [J].Crit Care Med , 2007,35(2): 526-31.
[4]望亭松,陆一鸣,戴然然,等.高渗氯化钠羟乙基淀粉40治疗失血性休克的临床研究[J],.上海第二医科大学学报2005,25(3):286-88.
[5] Gurfinkel V, Poggetti RS, Fontes B, et al.Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary inflammatory respinse caused by hemorrhagic shock[J].J Trauma, 2003,54(6):1137-45.
[6] Pascual JL, Khwaja KA, Ferri LE, et al.Hypertonic saline resuscitation arrenuates neutrophil lung sequestration and transmigration by diminutesishing leukocyte-endothelia interactions in a two-hit model of hemorrhagic shock and infection[J].J Trauma, 2003,54(1):121-130.
[7]陈世文,周晓平,胡小吾.高渗盐复合液对冷冻性脑损伤合并休克的治疗作用[J],中华神经医学杂志.2005,4(10):1002-1004.
[8] Pinto F C , Capone-Neto A , Prist R, et al . Volumme replacement with lactated Ringer’s or 3% hypertonic saline solution during combined experimental hemorrhagic schock and traumatic brain injury [J].J Trauma,2006,60(4):758-64.
[9] Bentsen G, Breivik H, Lundar T, et al. Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamaics in placebo-controlled study involing stable patients with subarachnoid hemorrhage [J].Crit Care Med,2006,34(12):2612-17.
[10]肖华平,古妙宁,肖金仿,等.高渗盐复合液治疗急性颅内高压伴失血性休克犬的实验研究[J] .广东医学,2008,3(29):392-94.
[11]肖诗铭,满晓波,邱秀华等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠肠缺血-再灌注损伤中L-选择素的表达和中性粒细胞浸润的影响中国医药导刊[J],2005,7(6):451-53.
[12]朱红军,于曙东,杨美菊,等.高渗高胶液体对兔肺挫伤合并失血性休克的疗效观察.江苏大学学报[J],2007,3(17):222-24.
[13]王勇,赵超英,钱琤等.复方高渗盐溶液对失血性休克大鼠脾脏细胞凋亡的影响[J].创伤外科杂志,2006,7(2):109-11.
[14]赵念峰,杨建香,黄爱杰,等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠凝血功能的影响[J].临床麻醉学杂志,2008,24(7):605-6.
[15]占丽芳,侯小敏,刘友坦等.高渗氯化钠羟乙基淀粉40注射液对大鼠全身高温模型血脑屏障通透性的影响[J].国际麻醉学与复苏杂志,2009,30(1):27-31.
[16] Battison C, Andrews P J, Graham C, et al. Randomized controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury [J].Crit Care Med,2005,33(1):196-202.
[17] Bender R, Breil M, Heister U, et al. Hypertonic saline during CPR: Feasibility and safety of a new protocol of fluid management during resuscitation[J]. Resuscitation.2007,72(1):74-81.
[18]李峰,孙华,韩旭东.不同液体对感染性休克早期液体复苏的影响研究[J].中国危重病急救医学,2008,20(8):472-75.
[19]郑琦涵,岳茂兴,李瑛.小剂量高渗氯化钠羟乙基淀粉40注射液在创伤性休克治疗中的疗效[J].创伤外科杂志,2008,10(5):465.
[20]刘友坦,黄绍农,古妙宁,等.高晶胶体液对体外循环热灌注治疗期间血液动力学和血气电解质的影响[J].南方医科大学学报,2008,28(9):160-2.
[21] Schroth M, Plank C, Meissner U, et al. An early bolus of hypertonic saline hydr oxyethyl starch improves long term outcome after global cerebral ischemia[J].Crit CareMed,2006,34(8):2194-200.
[2]肖华平,古妙宁,肖金仿,等.高渗盐复合液治疗急性颅内高压伴失血性休克犬的实验研究[J].广东医学,2008,3(29):392-94.
[3]肖诗铭,满晓波,邱秀华,等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠肠缺血-再灌注损伤中L-选择素的表达和中性粒细胞浸润的影响[J].中国医药导刊,2005,7(6):451-53.
[4] Longa E Z, Weinstein P R, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats [J].Stroke, 1989, 20 (1):84-91.
[5]廖维靖,刘淑红,范明线,等.线栓阻断大鼠大脑中动脉制作缺血性脑损伤模型的改良[J].中华物理医学与康复杂志,2002,24(6):6345-6348.
[6]尚进林,孙莉,梁浩等.过氧化物酶体增殖物激活受体1激动剂对小鼠局灶性脑缺血再灌注损伤的保护作用[J].中华神经科杂志,2009,42(3):190-194.
[7]邹景霞,李巧霞,陈学忠,等.脑缺血再灌注损伤的中医药防治进展[J].甘肃中医,2009,22(1):74-75.
[8] Bourekas EC, Slivka AP, Shah R, et a1.Intraarterial thrombolyic therapy with 3 hours of the onset of stroke [J].Neurosurgery, 2004, 54(1): 39-44.
[9] Dhandapani KM,Brann D W.Transforming growth factor-beta:a neuroprotecfive factor in cerebral isehemia [J].Cell Biochem Biophys, 2003,39(1): 13-22.
[10]李建生,马玉羡,郭剑峰.中医药防治脑缺血再灌注损伤的研究进展[J].河南中医药学刊,1999,14(2):6l一64.
[11] Toung T J, Chen C H, Lin C, et al. Osmothertapy with hypertonic saline attenuates water content in brain and extracerebral organs[J].Crit Care Med, 2007, 35(2):526-31.
[12]陈世文,周晓平.高渗盐溶液对脑外伤及合并休克的治疗作用[J].国外医学神经病学神经外科学分册,2004,31(3):241-244 .
[13] Ogden AT, Mayer SA, Connolly ES, et al.Hyperosmolar agent in neurosurgical practive the evolving role of hypertonic saline[J].Neurosurgery 2005, 57(2):207-215.
[14]李良东,黄志华,曾靖,等.DSS对脑缺血再灌注损伤的保护与抗氧化作用的关系[J].中风与神经疾病杂志,2009,(4):407-409.
[15]李良东,黄志华,黎晓,等.PBNA-413对脑缺血再灌注损伤时脑水肿及炎性细胞因子的影响[J].中药药理与临床,2009,23(1):30-31.
[16] Liu T, Clark R K, McDonnell PC, et al. Tumor necrosis factor-alpha expression in ischemic neurons[J]. Stroke, 1994,25(7):1481-8.
[17] Dempsey RJ, Baskaya MK, Dogan A. Attenuation of brain edema, blood-brain barrierbreakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate recepter antagonist, after experimental traumatic brain injury in rats[J]. Neurosurgery, 2000,47 (2):399～406.
[18]郑跃英,兰允平,祝胜美.大鼠脑缺血/再灌注损伤后梗死灶周围水通道蛋白4与血脑屏障通透性的动态变化[J].中国病理生理杂志,2008,24(8):1647-1649、1655.
[19] James HE. The effect of intravenous fluid replacement on the response to mannitol in experimental cerebral edema: an analysis of intracranial pressure, serum osmolality, serum electrolytes, and brain water content[J]. Acta Neurochir Suppl, 2006, 96: 125 - 9.
[20] Jones NC, Constantin D, Prior MJ, et al . The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression [J]. Eur J Neurosci, 2005, 21 (6): 1547 - 54.
[21]薛晶,韩冬,邓方,等.拉奉对脑缺血再灌注损伤保护作用机制的研究[J].中风与神经疾病杂志,2009,26(1)18-20.
[22] Saito A, Maier C M, Narasimhan P, et a1.Oxidative stress and neuronal death/survival signaling in cerebralischemia[J].Mol Neurobiol,2005,31(1-3):105-16.
[23] Yamawaki M, Sasaki N, Shimoyama M, et a1.Protective effect of edaravone against hypoxia—reoxygenation injury in rabbit cardiomyocytes [J].Br J Pharmacol,2004,142(3):618-26.
[24]吕平,郭芳,张目红,等.双苯氟嗪对脑缺血再灌注损伤后脑组织及血清中NO、NOS、iNOS的影响[J].中国药理学通报,2005,21(11):1340—1343.
[25]吕鸿燕,朱旭友,陈前芬.硫酸镁预处理对小鼠全脑缺血再灌注损伤后一氧化氮及一氧化氮合酶的影响[J].蚌埠医学院学报,2009,34(9)762-764.
[26] Tsai SK, Hung LM, Fu YT, et a1.Resveratrol neuroproteetive effects during focal cerebral ischemia injury via nitric oxide mechanism in rats[J].J Vase Surg,2007,46(2):346-53.
[27] xu J, He L, Ahmed SH, et al.Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells [J].Stroke,2000,31(7):1744—51.
[28]苗明山,张桂兰,张玉林.醒脑再造胶囊对大鼠血瘀性脑缺血模型脑组织的影响[J].中药药理与临床,2007,23(3):69-70.
[29]宋翠荣,杨艳梅,刘建辉,等.新生儿缺血缺氧性脑病生物学指标的研究进展[J].中外健康文摘,2009,6(11)237-238.
[30]贺勇,尤志瑶,周少华,等.短暂性脑缺血发作患者血清S- 100和神经元特异性烯醇化酶的测定及临床意义[J].实用医学杂志,2005,21(1):37-38.
[31] Abraha HD, Butterworth RJ, Bath PM, et al.Serum S-100 protein , relationship to clinical outcome in acute stroke [J].Ann Clin Biochem, 1997, 34(4):366-70.
[32] Wang S, Xu X, Gu L. Changes in the expression of C-fos & heat shock protein genes & blood flow velocity in the brain of rats undergoing myocardial ischaemia /reperfusion[J].Indian J Med Res, 2006, 123(2):131-38.
[33] Franklin TB, Krueger-Nang AM, Clarke DB, et a1.The role of heat shock proteins Hsp70 andHsp27 in cellular protection of the central nervous system[J].Int J Hyperthermia, 2005, 21(5):379- 92.
[34] Lee SH, Kwon H M, Kim Y J, et al. Effects of hsp70.l gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia [J]. Stroke, 2004,35(9):2195-9.
[1] Boldt J, Fluid choice for resuscitation of the trauma patient: a review of the physiological, pharmacological and clinical evidence [J]. Can J Anesth, 2004,51(5):500-513.
[2] Ogden A T, Mayer S A, Connolly E S, et al.Hyperosmolar agent in neurosurgical practice: the evolving role of hypertonic saline [J]. Neurosurgery, 2005, 57(2): 207-15.
[3] Toung T J, Chen C H, Lin C, et al.Osmothertapy with hypertonic saline attenuates water content in brain and extracerebral organs [J].Crit Care Med , 2007,35(2): 526-31.
[4]望亭松,陆一鸣,戴然然,等.高渗氯化钠羟乙基淀粉40治疗失血性休克的临床研究[J],.上海第二医科大学学报2005,25(3):286-88.
[5] Gurfinkel V, Poggetti RS, Fontes B, et al.Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary inflammatory respinse caused by hemorrhagic shock[J].J Trauma, 2003,54(6):1137-45.
[6] Pascual JL, Khwaja KA, Ferri LE, et al.Hypertonic saline resuscitation arrenuates neutrophil lung sequestration and transmigration by diminutesishing leukocyte-endothelia interactions in a two-hit model of hemorrhagic shock and infection[J].J Trauma, 2003,54(1):121-130.
[7]陈世文,周晓平,胡小吾.高渗盐复合液对冷冻性脑损伤合并休克的治疗作用[J],中华神经医学杂志.2005,4(10):1002-1004.
[8] Pinto F C , Capone-Neto A , Prist R, et al . Volumme replacement with lactated Ringer’s or 3% hypertonic saline solution during combined experimental hemorrhagic schock and traumatic brain injury [J].J Trauma,2006,60(4):758-64.
[9] Bentsen G, Breivik H, Lundar T, et al. Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamaics in placebo-controlled study involing stable patients with subarachnoid hemorrhage [J].Crit Care Med,2006,34(12):2612-17.
[10]肖华平,古妙宁,肖金仿,等.高渗盐复合液治疗急性颅内高压伴失血性休克犬的实验研究[J] .广东医学,2008,3(29):392-94.
[11]肖诗铭,满晓波,邱秀华等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠肠缺血-再灌注损伤中L-选择素的表达和中性粒细胞浸润的影响中国医药导刊[J],2005,7(6):451-53.
[12]朱红军,于曙东,杨美菊,等.高渗高胶液体对兔肺挫伤合并失血性休克的疗效观察.江苏大学学报[J],2007,3(17):222-24.
[13]王勇,赵超英,钱琤等.复方高渗盐溶液对失血性休克大鼠脾脏细胞凋亡的影响[J].创伤外科杂志,2006,7(2):109-11.
[14]赵念峰,杨建香,黄爱杰,等.高渗氯化钠羟乙基淀粉40注射液对失血性休克大鼠凝血功能的影响[J].临床麻醉学杂志,2008,24(7):605-6.
[15]占丽芳,侯小敏,刘友坦等.高渗氯化钠羟乙基淀粉40注射液对大鼠全身高温模型血脑屏障通透性的影响[J].国际麻醉学与复苏杂志,2009,30(1):27-31.
[16] Battison C, Andrews P J, Graham C, et al. Randomized controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury [J].Crit Care Med,2005,33(1):196-202.
[17] Bender R, Breil M, Heister U, et al. Hypertonic saline during CPR: Feasibility and safety of a new protocol of fluid management during resuscitation[J]. Resuscitation.2007,72(1):74-81.
[18]李峰,孙华,韩旭东.不同液体对感染性休克早期液体复苏的影响研究[J].中国危重病急救医学,2008,20(8):472-75.
[19]郑琦涵,岳茂兴,李瑛.小剂量高渗氯化钠羟乙基淀粉40注射液在创伤性休克治疗中的疗效[J].创伤外科杂志,2008,10(5):465.
[20]刘友坦,黄绍农,古妙宁,等.高晶胶体液对体外循环热灌注治疗期间血液动力学和血气电解质的影响[J].南方医科大学学报,2008,28(9):160-2.
[21] Schroth M, Plank C, Meissner U, et al. An early bolus of hypertonic saline hydr oxyethyl starch improves long term outcome after global cerebral ischemia[J].Crit CareMed,2006,34(8):2194-200.