枕大池注入尼莫地平对兔蛛网膜下腔出血后海马线粒体通路的影响  

The effect of nimodipine injecting into cisterna magna on mitochondrial pathway in hippocampus of rabbit model of subarachnoid hemorrhage

作　　者：丁浩[1] 符永健[2] 张松松[2] 陈金[1] 施贤清[2] DING Hao;FU Yong-jian;ZHANG Song-song;CHEN Jin;SHI Xian-qing(Guizhou Medical University, Guiyang 550004, China;Department of ICU, Guizhou Provincal People Hospital)

机构地区：[1]贵州医科大学,550004 [2]贵州省人民医院ICU

出　　处：《天津医药》2017年第5期468-471,共4页Tianjin Medical Journal

基　　金：贵州省科学技术基金计划(黔科合基础[2016]1095)

摘　　要：目的探讨枕大池注入尼莫地平对兔蛛网膜下腔出血(SAH)后海马线粒体通路的影响。方法 18只新西兰大白兔随机分为假手术组(Sham组)、SAH组、尼莫地平组(ND组),每组6只。各组均在麻醉下行手术操作,SAH和ND组取自体动脉血(1 mL/kg)注入枕大池建模,Sham组注入等剂量生理盐水。30 min后ND组再次经枕大池注入尼莫地平(1 mg/kg),SAH组、Sham组注入等体积生理盐水。SAH后72 h进行摄食量和神经功能损害分级评价后处死动物,取海马组织,qRT-PCR检测Bcl-2、Bax、Caspase-3、Cyt-C mRNA表达,Western blot检测Caspase-3、Cyt-C蛋白表达。结果与Sham组相比,SAH、ND组动物摄食量减少,出现不同程度的神经功能损害,Bcl-2/Bax降低;但Bcl-2、Bax mRNA,Caspase-3、Cyt-C mRNA及蛋白表达升高(P<0.05)。与SAH组相比,ND组摄食量及神经功能损害差异无统计学意义(P>0.05),但Bcl-2 mRNA表达升高,Bax mRNA表达降低,Bcl-2/Bax升高;Caspase-3、Cyt-C mRNA及蛋白表达降低(P<0.05)。结论尼莫地平可通过抑制SAH后海马线粒体通路激活和减少细胞凋亡来发挥脑保护作用。Objective To investigate the effect of nimodipine(ND)injecting into cisterna magna on the mitochondrialpathway in hippocampus in rabbit model of subarachnoid hemorrhage(SAH).Methods Eighteen New Zealand whiterabbits were randomly allocated to Sham group,SAH group and ND group,six in each group.All the animals underwentoperation under anaesthesia.One mL/kg autologous non-heparinized arterial blood was injected into cisterna magna in SAHgroup and ND group,and the same dosage of saline was injected into cisterna magna in Sham group.Thirty minutes afterinjection,1mg/kg nimodipine was injected into cisterna magna in ND group,and equal-volume of saline was injected intocisterna magna in Sham group and SAH group.All the animals were assessed for the grade of food intake and neurologicalimpairment,and rats were killed72hours after SAH.Their hippocampus were processed for detecting the expressions of Bcl-2,Bax,Caspase-3and Cyt-C mRNA by qRT-PCR.The protein expressions of Caspase-3and Cyt-C were detected byWestern blot assay.Results Compared with the Sham group,there were lower grade of food intake,varying degrees ofneurological impairment and lower ratio of Bcl-2/Bax,while the mRNA levels of Bcl-2,Bax,Caspase-3and Cyt-C andprotein levels of Caspase-3and Cyt-C showed elevated expressions in SAH group and ND group(P<0.05).Compared withSAH group,there were no significant differences in the score of food intake and neurological impairment in the ND group(P>0.05).There were higher ratio of Bcl-2/Bax and expression levels of Bcl-2mRNA and lower expression levels of Bax mRNA,Caspase-3and Cyt-C mRNA and proteins in ND group than those in SAH group(P<0.05).Conclusion Nimodipine playsa protective role in inhibiting the activity of mitochondrial pathway in hippocampus after subarachnoid hemorrhage.

关 键 词：尼莫地平 蛛网膜下腔出血 细胞凋亡 线粒体通路 枕大池 

分 类 号：R743.35[医药卫生—神经病学与精神病学]