【摘要】 目的探讨大鼠局灶性脑缺血2h再灌注6h神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)来源的一氧化氮(nitric oxide,NO)和过氧亚硝基阴离子(peroxymtrite,ONOO~-)对Caspase-3蛋白表达的影响。方法 48只健康雄性SD大鼠随机分为假手术组、单纯缺血/再灌注组、溶剂对照组和7-硝基吲唑(12.5、25、50mg/kg)组。闭塞大鼠左侧大脑中动脉造成局灶性脑缺血模型。给予选择性nNOS抑制剂7-硝基吲唑(12.5,25,50mg/kg)组,采用硝酸还原酶法检测脑组织NO含量、流式细胞术检测硝基酪氨酸表达、免疫组织化学法检测Caspase-3蛋白表达的变化。结果与假手术组相比,单纯缺血/再灌注组及溶剂对照组,脑组织NO含量,硝基酪氨酸含量及Caspase-3表达均升高(P<0.01)。与溶剂对照组比较,腹腔注入7硝基吲唑抑制nNOS活性可使Caspase-3蛋白表达降低(P<0.05)。结论大鼠局灶脑缺血再灌注过程中,nNOS来源的NO/ONOO可促进Caspase-3蛋白表达,这可能是nNOS活性增加促进细胞凋亡的机制之一。更多还原

【Abstract】 Objective To investigate the effects of nNOS-derived nitric oxide(NO)/ peroxynitrite(ONOO~-)on the expression of Caspase-3 protein following focal cerebral ischemia and reperfusion in rats which were sacrificed at 6h of reperfusion after 2 h of ischemia. Methods Fourty-eight healthy male SD rats were randomly divided into 6 groups,which were sham group,simple ischemia/reperfusion group,vehicle group,7-nitroindazole(12.5,25,50 mg/ kg)groups.Focal cerebral ischemic model was induced by the occlusion of left middle cerebral artery.7-nitroindazole,a selective inhibitor of nNOS,was given intraperitoneally.The content of NO was measured by nitriate reductase method.The expression of NT was examined by flow cytometry.The Caspase-3 expression was detected immunohistochemically.Results Cerebral NO content,nitrotyrosine content and expression of Caspase-3 in simple cerebral ischemia/reperfusion group and vehicle group were all increased(P<0.01)when compared with those of sham group. The expression of Caspase-3 protein was remarkably lower in 7-nitroindazole groups than vehicle group.Conclusion NO/ONOO~-derived from nNOS might promote apoptosis following focal cerebral ischemia and reperfusion via upregulating Caspase-3 expression.更多还原