雌激素干扰亚急性MPTP小鼠PD模型黑质纹状体DRP1表达  

Estrogen Interwention Effects the Nigrostriatal DRP1 Expression in Subacute MPTP PD Mice Model

作　　者：周洁[1] 罗海彦[1] Zhou Jie;Luo Haiyan(Department of Neurology, Chongqing Medical University, Chongqing, 400016)

机构地区：[1]重庆医科大学附属医院

出　　处：《基因组学与应用生物学》2018年第4期1705-1712,共8页Genomics and Applied Biology

基　　金：重庆市集成示范计划项目(CSTC2015JCSF10006)资助

摘　　要：探究1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的亚急性帕金森病（PD）模型小鼠黑质纹状体神经元动力相关蛋白1（DRP1）的表达以及在雌激素的干预下所发生的变化,从而进一步探讨雌激素对帕金森病的保护作用以及在线粒体动力学方面的作用机制和原理。本研究将C57/BL小鼠随机分配为4组：模型组（MPTP）、对照组（生理盐水）、干预组（Estrogen＋MPTP）、干预对照组（Estrogen）,腹腔注射一定浓度的MPTP,造模成功后,灌胃给药戊酸雌二醇,一段时间后观察小鼠行为学变化,采用双标免疫荧光检测各组的DRP1和GFAP在小鼠脑黑质纹状体神经元的表达差异,以及采用免疫组织化学和免疫蛋白印迹法检测PD小鼠黑质纹状体DRP1表达的变化以及给予雌激素干预后对上述变化的影响。研究显示,与对照组相比,模型组（MPTP）小鼠表现出典型的PD症状,脑黑质纹状体神经元DRP1明显增多;经雌激素干预处理后,小鼠PD症状有所减轻,免疫组织化学和免疫蛋白印迹法检测的各组脑黑质纹状体DRP1的表达的变化趋势一致,干预组的DRP1表达量明显低于模型组,高于干预对照组,并且对照组和干预组的DRP1表达量无显著性差异。说明一定浓度的雌激素对正常的小鼠无明显作用,而对患PD的小鼠,雌激素能明显改善其病症,因此,雌激素对帕金森病起着一定的保护作用,其潜在的机制可能与雌激素降低了黑质纹状体神经元DRP1的表达从而减少了线粒体异常分裂有关,但是具体的原理还需要进一步的深入研究。Study on 1-Methy1-4-Pheny1-1, 2, 3, 6-etrahydropyridine（MTPT） induced subacute Parkinson disease（PD） mouse model of nigrostriatal neurons dynamin related protein 1（DRP1） expression and changes in estrogen intervention, in order to further explore the protective effects of estrogen on Parkinson’s disease and in the role of mitochondrial dynamics the mechanism and principle. In this study, C57/BL mice were randomly divided into four groups： model group（MPTP）, control group（saline）, intervention group（Estrogen＋MPTP）, control group（Estrogen）,intraperitoneal injection of MPTP at a certain concentration, after the success of modeling, intragastric administration of estradiol valerate, after a period of observation in mice the behavioral changes, using double immunofluorescence to detect DRP1 and GFAP expression differences in mouse brain nigrostriatal neurons, and the expression of the nigrostriatal DRP1 detection of PD mice by immunohistochemistry and Western blotting and the changes in estrogen affects the prognosis of the change of dry. The results showed that compared with the control group, the model group（MPTP） mice showed typical symptoms of PD, cerebral nigrostriatal DRP1 neurons increased significantly; after estrogen treatment, mice PD symptoms eased, the same trend of expression of each cerebral nigrostriatal DRP1 detected by immunohistochemistry and Western blotting. The intervention group, the expression of DRP1 was significantly lower than that of model group was higher than that of control group,intervention group and intervention group, and the expression of DRP1 had no significant difference. That a certain concentration of estrogen had no effect on normal mice and in mice with PD, estrogen can significantly improve the symptoms, therefore, estrogen plays a protective role in Parkinson’s disease and its potential mechanism may be related to estrogen decreased the expression of nigrostriatal neurons DRP1 reduced mitochondrial dysfunction division. However, the spe

关 键 词：帕金森病 MPTP 雌激素 DRP1 线粒体动力学 

分 类 号：R-332[医药卫生] R742.5