Mdivi-1对匹鲁卡品致痫大鼠海马神经元保护作用及其机制研究  

Protective effect of Mdivi-1 on hippocampal neurons in epileptic rats induced by pilocarpine and its mechanism

作　　者：甘露 周弟弥 张磊 陈琳 Gan Lu;Zhou Dimi;Zhang Lei(Dept of Internal Medicine-Neurology,The Second Hospital of University China,Hengyang 421001)

机构地区：[1]南华大学附属第二医院神经内科,衡阳421001

出　　处：《安徽医科大学学报》2020年第5期751-756,共6页Acta Universitatis Medicinalis Anhui

基　　金：湖南省医药卫生科研计划项目(编号:B2014-056)。

摘　　要：目的研究线粒体分裂蛋白抑制剂(Mdivi-1)对癫痫大鼠行为学及海马区线粒体动力相关蛋白1(DRP1)、平衡型核苷转运载体1(ENT1)蛋白的影响。方法20只雄性SD大鼠随机均分为正常组、模型组、DMSO组、Mdivi-1组。观察各组大鼠行为学改变,透射电镜观察脑组织结构变化;免疫组化及免疫荧光法检测各组大鼠海马区DRP1表达;Western blot检测各组大鼠海马区DRP1、ENT1蛋白变化。结果与模型组或DMSO组相比,Mdivi-1组大鼠癫痫发作潜伏期明显增加而发作频率下降(P<0.05);电镜观察结果显示,模型组部分内外膜崩解,线粒体明显破坏、肿胀而Mdivi-1组损伤情况减轻;免疫组化结果显示,模型组大鼠脑组织海马区DRP1阳性细胞数增多,而Mdivi-1组阳性细胞数下降(P<0.05);免疫荧光显示,DRP1在海马神经元中有表达;Western blot结果显示,与正常组相比,DMSO和模型组中ENT1、DRP1蛋白表达升高,而Mdivi-1组中ENT1、DRP1蛋白表达下降(P<0.05)。结论Mdivi-1能靶向阻断DRP1,调控线粒体动力学平衡,从而影响ENT1表达,对海马神经元具有神经保护的作用。Objective To study the effects of mitochondrial division inhibitor(Mdivi-1)on behavior,dynamin-related protein 1(DRP1)and equilibrative nucleoside transporter-1(ENT1)proteins in hippocampus of epileptic rats.Methods Twenty male SD rats were randomly divided into normal group,model group,DMSO group and Mdivi-1 group(5 rats in each group).Behavioral changes of rats in each group were observed,and brain tissue structure changes were observed by transmission electron microscopy.The DRP1 expression in hippocampus of rats was detected by immunohistochemistry and immunofluorescence.Changes of DRP1 and ENT1 proteins in hippocampus of rats in each group were detected by Western blot.Results Compared with model group or DMSO group,the latency of epileptic seizures in Mdivi-1 group increased and the frequency of epileptic seizures decreased(P<0.05).The results of electron microscopy showed that the epilepsy group had partial disintegration of inner and outer membranes,obvious destruction and swelling of mitochondria,while the mdivi-1 group had less damage.Immunohistochemical results showed that the number of DRP1 positive cells in hippocampus increased in model group while decreased in Mdivi-1 group(P<0.05).Immunofluorescence showed that DRP1 was expressed in hippocampal neurons.Western blot results showed that the expression of ENT1 and DRP1 protein in DMSO and model group was higher than that in normal control group,while the expression of ENT1 and DRP1 protein in Mdivi-1 group was lower(P<0.05).Conclusion Mdivi-1 can restrain DRP1 and regulate the dynamic balance of mitochondria,thus affecting the expression of ENT1,which has neuroprotective effect on hippocampal neurons.

关 键 词：癫痫 海马神经元 平衡型核苷转运载体-1 线粒体分裂蛋白抑制剂-1 动力相关蛋白1 

分 类 号：R741.02[医药卫生—神经病学与精神病学]