“抗帕颗粒”通过泛素-蛋白酶体途径对帕金森小鼠α-syn异常聚集的影响  

The effect of‘Anti-Parkinson granule’on the abnormal aggregation of α-syn through ubiquitin proteasome system in the Parkinson disease mouse model

作　　者：颜静 赵晓晖[1] 王永兵[2] 张丽娅 刘慧琴[1] Yan Jing;Zhao Xiaohui;Wang Yongbing;Zhang Liya;Liu Huiqin(Department of Neurology,the Shanghai Pudong New Area People’s Hospital,Shanghai 201200,China)

机构地区：[1]上海市浦东新区人民医院神内二科,上海201200 [2]上海市浦东新区人民医院普外科,上海201200

出　　处：《脑与神经疾病杂志》2020年第11期692-697,共6页Journal of Brain and Nervous Diseases

基　　金：上海市浦东新区科委科技发展基金民生科研专项(PKJ2017-Y32);上海市浦东新区医学重点学科建设项目(PWZxk207-11)

摘　　要：目的探讨中药"抗帕颗粒"通过泛素-蛋白酶体系统(UPS)影响帕金森病(PD)小鼠黑质纹状体区α-突触共核蛋白(α-syn)异常聚集的可能机制。方法采用C57BL/6小鼠作为实验动物,1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)腹腔注射制模,随机分为:Ⅰ组(正常对照组)、Ⅱ组(PD对照组)和Ⅲ组(PD"抗帕颗粒"干预组),每组30只。第Ⅲ组"抗帕颗粒"灌胃浓度800mg·mL^-1,剂量40mg·kg^-1·d^-1,第Ⅰ、Ⅱ组予生理盐水1ml·d^-1灌胃,分笼喂养4个月。处死后取标本Western blotting法检测各组黑质纹状体区α-syn、泛素羧基端水解酶-1(UCH-1)、Parkin蛋白量的表达。结果①90只小鼠中87只存活4个月,分别为第Ⅱ组死亡2只,第Ⅲ组死亡1只;第Ⅱ组13.33%(4/30)、第Ⅲ组10.00%(3/30)在制模7~14d内出现一过性低体温(肛温<33.0℃)。两组以上表现及持续时间无显著性差异,P>0.05;②α-syn蛋白定量:第Ⅰ组、Ⅱ组比较,P<0.01;第Ⅰ组、Ⅲ组比较,P<0.05;第Ⅱ组与第Ⅲ组比较,P<0.05;③UCH-1、Parkin蛋白定量:第Ⅰ组、Ⅱ组比较,分别为P<0.01、P<0.05;第Ⅰ组、Ⅲ组比较,分别为P<0.01、P<0.05;第Ⅱ组与第Ⅲ组比较,分别为P<0.001、P<0.01。结论"抗帕颗粒"通过UPS途径抑制PD小鼠黑质纹状体区α-syn的异常聚集,其中阻断氧化应激反应可能是这种保护作用的关键机制,但不能完全逆转PD的病理改变。Objective To find out the possible mechanism of that‘Anti-Parkinson disease granule’makes effects on the abnormal accumulation ofα-syn through UPS in the Parkinson mouse model.Methods As animals for experiment,C57 BL/6 mouse were intraperitoneally injected by MPTP(40 mg·kg^-1·d^-1×7)to make PD model,and they were divided into three groups randomly:groupⅠ(normal control group),groupⅡ(PD model control group)and groupⅢ(PD model intervention group)with 30 mouse in each group.The groupⅢwere gavaged with‘antiParkinson granule’(40 mg·kg^-1·d^-1)for 4 months.Using Western blotting,the expression levels ofα-synuclein(α-syn),ubiquitin carboxyl terminal hydrolase-1(UCH-1)and Parkin proteins in the substantia nigra striatum area of each group were compared and analyzed at the end of the fourth month.Results①After 4 months,87 mouse were survived,2 died in the groupⅡand 1 died in the groupⅢ.13.33 percent(4/30)of groupⅡ,10.00 percent(3/30)of groupⅢoccured hypothermy during the 7-14 days.There was no significant difference between the two groups,P>0.05;②The expression ofα-syn protein:the comparison between groupⅠand groupⅡwas P<0.01,between groupⅠand groupⅢwas P<0.05,and between groupⅡand groupⅢwas P<0.05.③The expression of UCH-1 and Parkin proteins:between groupⅠand groupⅡ,P<0.01 and P<0.05 respectively,between groupⅠand groupⅢwere P<0.01 and P<0.05,and between groupⅡand groupⅢwere P<0.001 and P<0.01.Conclusion‘Anti-Parkinson granule’has an inhibitory effect on the abnormal aggregation ofα-syn in the substantia nigra striatumregion in PD mouse,which is partly related to the improvement of UPS function.The protective effect can be delivered by blocking oxidative stress response.Howerever,‘Anti-Parkinson granule’can’t reverse the pathology of PD completely.

关 键 词：帕金森病 小鼠模型 “抗帕颗粒” 泛素-蛋白酶体系统 α-突触共核蛋白 

分 类 号：R285.5[医药卫生—中药学]