雷帕霉素对帕金森病小鼠模型线粒体呼吸功能及跨膜电位的影响  

Effects of rapamycin on mitochondrial respiratory function and transmembrane potential in Parkinson's disease mouse model

作　　者：马琳[1] 付廷飞 刘香锟 郭记宏[4] MA Lin;FU Ting-fei;LIU Xiang-kun;GUO Ji-hong(Department of Neurology, the First Hospital of Handan, Hebei 056002, China)

机构地区：[1]邯郸市第一医院神经内二科,河北056002 [2]河北省邯郸军分区卫生所 [3]冀中能源峰峰矿区总医院老年病科 [4]河北医科大学第一医院神经内科

出　　处：《脑与神经疾病杂志》2017年第4期212-215,共4页Journal of Brain and Nervous Diseases

基　　金：河北省2016年度医学科学研究重点课题计划(20160340)

摘　　要：目的探讨雷帕霉素(RAPA)对帕金森病(PD)小鼠模型线粒体呼吸功能及其跨膜电位的影响。方法将54只昆明小鼠随机分为3组:空白组,模型组,用药组。空白对照组不进行任何处理;模型组与用药组均采用皮下注射1-甲基-4-苯基四氢吡啶(MPTP)法制作PD模型;用药组在制备模型前、中、后持续给予RAPA灌胃给药,空白组与模型组同时给予同体积的生理盐水。给药结束后对各组小鼠采用自主活动及滚轴运动进行行为学评分,高效液相-电化学法(HPLC-ECD)检测黑质DA含量,比色法定量检测线粒体复合物Ⅰ活性,应用流式细胞仪分析线粒体的跨膜电位。结果与空白组比较,模型组、用药组的行为学成绩、黑质多巴胺水平、复合物Ⅰ活性、跨膜电位均显著下降(P<0.05);而与模型组比较,给用药组的各项指标均显著改善(P<0.05)。结论 RAPA可以有效改善PD小鼠模型行为学表现,其机制可能与改善线粒体膜电位和线粒体复合物活性有关。Objective To investigate the effects of rapamycin(RAPA)on mitochondrial respiratory function and transmembrane potential in mouse model of Parkinson's disease(PD).Method Fifty-four Kunming mice were randomly divided into3groups:blank group,model group,treatment group.The mice in blank group were not given any treatment,while the mice in model group and treatment group were treated with subcutaneous injection of1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)making PD model.Intragastric administration of rapamycin was continued given before,during and after the model preparation to the treatment group,as the same volume of saline was givento the other two groups at the same time.After administration,the behavior were tested with spontaneous activity and rolling test,the content of dopamine were detected by high performance liquid chromatography with electrochemical detector(HPLC-ECD),the activity of mitochondrial complexⅠand the transmembrane potential of mitochondria were respectively detected by quantitative colorimetric method and flow cytometry in three groups.Results Behavioral scores,substantia nigra dopamine levels,mitochondrial complex I activity,transmembrane potential of mice in model group and treatment group were all significantly decreased compared with that of the blank group(P<0.05);andall kinds of indexes in the treatment group were significantly improved compared to the model group(P<0.05).Conclusion Rapamycin could effectively improve the behavior disorder of PD mice,and its mechanism may be related to the improvement of mitochondrial membrane potential and mitochondrial complex activity.

关 键 词：雷帕霉素 帕金森病 线粒体 膜电位 

分 类 号：R742[医药卫生—神经病学与精神病学]