大鼠局灶性脑缺血再灌注中nNOS源性NO对Bcl-2、Bax表达的影响

为研究大鼠局灶性脑缺血再灌注早期神经元型一氧化氮合酶(nNOS)来源的一氧化氮(NO)和过氧亚硝基阴离子(ONOO-)对Bcl-2和Bax蛋白表达的影响,本实验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,应用免疫组化法检测Bcl-2和Bax蛋白表达的变化。结果表明:50mg/kg、25mg/kg剂量的7-硝基吲唑可使Bcl-2蛋白表达升高,Bax表达降低。提示:局灶性脑缺血再灌注早期,nNOS来源的NO可能通过下调Bcl-2、上调Bax促进细胞凋亡的发生。

EFFECTS OF nNOS-DERIVED NO ON Bcl-2 AND Bax PROTEIN EXPRESSION FOLLOWING FOCAL CEREBRAL ISCHEMIA AND REPERFUSION IN RATS

The effects of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) and peroxynitrite (ONOO~-)on Bcl-2 and Bax protein expression were investigated following focal cerebral ischemia and reperfusion in rats. Focal cerebral ischemic model was developed by the occlusion of left middle cerebral artery. 7-nitroindazole, a selective inhibitor of nNOS, was given intraperitoneally. The rats were sacrificed at 6 h of reperfusion after 2 h of ischemia. The Bcl-2 and Bax expression were detected immunohistochemically. The expression of Bcl-2 protein was remarkably higher while that of Bax was lower in 50 mg/kg and 25 mg/kg 7-nitroindazole groups than vehicle group. These results indicate that NO derived from nNOS might promote apoptosis in the early stage of cerebral ischemia via upregulating Bax and downregulating Bcl-2 expression.