线粒体分裂蛋白抑制剂在大鼠脑缺血再灌注损伤中的作用及其机制(英文)  

Effects of Mitochondrial Division Inhibitor(mdivi-1) on Rats Following Cerebral Ischemia/Reperfusion Injury and Its Mechanism

作　　者：张宁[1] 王士雷[1] 李淑虹[1] 李瑜[1] 王鹏[1] 贾长新[1] 

机构地区：[1]青岛大学医学院附属医院麻醉科,山东青岛266003

出　　处：《现代生物医学进展》2013年第18期3410-3414,共5页Progress in Modern Biomedicine

基　　金：Natural Science Foundation of China(30972855)~~

摘　　要：目的:观察线粒体分裂蛋白抑制剂在大鼠脑缺血再灌注损伤中的作用,并初步探讨其在线粒体凋亡途径中的作用机制。方法:雄性Wistar大鼠48只,体重250～300 g,随机分为三组(n=16):假手术组(Sham组)、脑缺血再灌注组(I/R组)和mdivi-1预处理组(mdivi-1组),线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,缺血2小时,再灌注24小时后应用流式细胞术检测神经元凋亡;Western blot法检测Cyt C蛋白的表达;RT-PCR法检测Cyt C mRNA的表达。结果:与Sham组比较,I/R组神经细胞凋亡率与Cyt C蛋白以及mRNA表达水平显著升高(P<0.01)。应用mdivi-1预处理后细胞凋亡率与Cyt C蛋白以及mRNA表达水平明显降低(P<0.01)。结论:线粒体分裂蛋白抑制剂可以明显减轻脑缺血再灌注损伤,其作用机制可能通过阻断线粒体-细胞色素C途径来抑制细胞凋亡。Objective：To investigate the protective effects of mitochondrial division inhibitor mdivi-1 on cerebral ischemia/reperfusion（I/R） in rats and the possible mechanism about neuronal apoptosis by mitochondria signaling pathways.Methods：48 Wistar rats were randomly and equally divided into the Sham-operated group（Sham）,ischemia/reperfusion group（I/R） and mitochondrial division inhibitor pre-conditioning group（mdivi-1）,with 16 rats in each group.The ischemia/ reperfusion model was performed by thread occlusion of middle cerebral artery for 2 h,then 24 h reperfusion.Neuronal apoptosis were detected by flow cytometry,the protein level of Cytochrome C in the cerebral issue was detected by western blot,and the mRNA expression was measured by semiquantitative reverse transcriptase polymerase chain reaction（RT-PCR）.Results：The apoptosis rate and the expression of Cytochrome C were significantly higher in the I/R group than those of Sham group.Preconditioning of mdivi-1 could significantly increas neurocyte survival and decreas the apoptosis rate as well as down-regulat the expression of Cytochrome C.Conclusion：Mitochondrial division inhibitor mdivi-1 protects the cerebral against ischemia/ reperfusion injury,and mitochondria-Cytochrome C mediated apoptotic pathway may plays an important role in the occurrence of steatosis.

关 键 词：脑缺血 再灌注损伤 细胞凋亡 细胞色素C 线粒体分裂 

分 类 号：Q95-3[生物学—动物学] R743[医药卫生—神经病学与精神病学]