【摘要】 目的观察外源性一氧化氮(NO)供体硝普钠(SNP)和亚硝基谷胱甘肽(GSNO)对脑缺血/再灌注过程中c-jun N末端激酶3(JNK3)磷酸化的影响,及其对再灌注海马CA1区锥体神经元的作用。方法采用四动脉结扎法建立大鼠全脑缺血模型。SNP(5 mg/kg)溶于生理盐水,间隔1.5 h分别腹腔注射3次,第1次注射时间在全脑缺血前30 min。GSNO(100μg/kg)溶于生理盐水,缺血前20 min于侧脑室注射给药。大鼠随机分为假手术组、缺血/再灌注组、缺血/再灌注溶剂对照组、缺血/再灌注给予SNP组和缺血/再灌注给予GSNO组,缺血15 min后分别灌注1天或5天。利用免疫印迹、免疫沉淀和焦油紫染色法检测相关蛋白的表达、磷酸化水平及神经元细胞的存活。结果给予SNP组和GSNO组与生理盐水对照组相比,能够显著抑制脑缺血/再灌注过程中JNK3的磷酸化,并且能显著提高再灌注过程中海马CA1区锥体神经元的存活。结论外源性NO供体能够抑制脑缺血/再灌注过程中JNK3的磷酸化,进一步对海马CA1区锥体神经元发挥了保护作用。本研究为外源性NO对脑卒中的有效治疗提供了参考价值。更多还原

【Abstract】 Objective To observe the effect of exogenous nitric oxide(NO) donors sodium nitropreside(SNP) and S-nitrosoglutathione(GSNO) on the phosphorylation of c-jun N-terminal kinase 3(JNK3) during brain ischemia/reperfusion and on the reperfused hippocampal CA1 pyramidal neurons.Methods Rats were induced by the four-vessel occlusion method(4-VO) to establish rat model of global ischemia.The rats were injected with SNP dissolved in saline at a dose of 5 mg/kg,three times at an internal of 1.5 h,i.p.,with the first injection given 30 min before ischemia.GSNO 100 μg/kg,dissolved in saline,was administrated intracerebroventricularly 20 min prior to ischemia.Rats were randomly assigned to 5 groups: sham group,ischemia/reperfusion(I/R) group,I/R solvent(saline) control group,I/R drug test(SNP) group and I/R drug test(GSNO) group.Reperfusion was allowed for 1 day or 5 days following transient brain ischemia of 15 min.Immunoblot(IB),immunoprecipitation(IP) and Cresyl Violet staining were performed to examine the expression and phosphorylation of relevant proteins and the survival of hippocampal neurons.Results Compared with saline group,treatment with SNP and GSNO groups dramatically depressed the phosphorylation of JNK3 and remarkably improved the survival of hippocampal CA1 pyramidal neurons,following reperfusion.Conclusions Exogenous NO donors can inhibit phosphorylation of JNK3 during brain ischemia/reperfusion,hence the neuroprotective effect on reperfused hippocampal CA1 pyramidal neurons.更多还原