复方地黄方调控GSK3β信号转导通路缓解帕金森病异动症模型大鼠的机制研究  

Study on Mechanism of Compound Formula Rehmannia on Remission of Rats Model of Levodopa-Induced Dyskinesia by Regulation of Gsk3β Signal Transduction Pathway

作　　者：滕龙[1] 洪芳[2] 何建成[2] 任璇璇[1] 杨敏春[1] TENG Long;HONG Fang;HE Jiancheng;REN Xuanxuan;YANG Minchun(Zhejiang Hospital, Hangzhou 310013, Zhejiang, China;Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)

机构地区：[1]浙江医院,浙江杭州310013 [2]上海中医药大学,上海201203

出　　处：《中华中医药学刊》2018年第4期815-818,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81573899);浙江省自然科学基金项目(LY15H270001,LY18H270015);上海市生物医药领域科技支撑项目(16401902400);上海市卫生局中医药科研基金项目(2012J009A);上海市卫生计生委科研基金项目(20144Y0151);浙江省中医药优秀青年人才基金项目(2016ZQ005);上海中医药大学预算内科研项目(2013JW25)

摘　　要：目的：探讨复方地黄方对帕金森病（PD）异动症（LID）模型大鼠GSK3β信号转导通路的影响。方法：采用6-羟基多巴胺（6-OHDA）偏侧损毁黑质制备PD大鼠模型,在成功制备PD大鼠模型基础上,腹腔注射左旋多巴＋苄丝阱制备LID大鼠模型。将大鼠随机分为正常对照组、假手术组、PD组、LID组、复方地黄方组,在治疗4周后取纹状体,应用Real-time PCR和Western blot测定各组大鼠纹状体内GSK3βmRNA、GSK3β蛋白及pGSK3β表达及磷酸化情况。结果：PD组和LID组大鼠纹状体中GSK3βmRNA和GSK3β蛋白相对表达水平较正常对照组、假手术组均显著升高（P〈0.01）,且LID组显著高于PD组（P〈0.01）,复方地黄方干预后其GSK3βmRNA和GSK3β蛋白相对表达水平显著降低（P〈0.01）。PD组和LID组大鼠纹状体中p-GSK3β（phospho S9）蛋白相对表达水平较正常对照组、假手术组均显著降低（P〈0.01）,且LID组显著低于PD组（P〈0.01）,复方地黄方干预后其p-GSK3β（phospho S9）蛋白相对表达水平显著升高（P〈0.01）。结论：复方地黄方可能通过调控GSK3β信号通路,缓解GSK3β蛋白的激活,对β-catenin磷酸化作用减弱,游离的β-catenin转移进核内,与结合蛋白一起触发下游α-syn,使α-syn异常聚集和错误折叠受限,影响细胞凋亡,从而缓解帕金森病及异动症。Objective： To investigate the effect of Compound Formula Rehmannia on GSK3β signal transduction pathway in rats of LID. Methods： We prepared Parkinson＇s disease model rats to receive injection of 6-hydroxydopamine into the left substantia nigra. Parkinson＇s disease model rats were intraperitoneally injected with levodopa and benserazide to produce a model of levodopa-induced dyskinesia. Rats were randomly divided into control,sham,PD model,LID model and Compound Formula Rehmannia groups. After 4 weeks of treatment,the striatum of the rats were removed,and we used Real-time PCR and Western blot to determine the expressions of GSK3βmRNA,GSK3β protein and p-GSK3β in striatum of rats. Results： The expression of GSK3βmRNA and GSK3β protein in striatum of PD and LID group significantly increased than that of the normal control and sham group（ P 〈0. 01） and that of LID group was significantly increased than that of the PD group（ P 〈0. 01） and the expressions of GSK3βmRNA and GSK3β protein significantly decreased after treatment with Compound Formula Rehmannia（ P 〈0. 01）. The expression of p-GSK3β（ phospho S9） protein in the striatum of PD and LID group significantly reduced than those of the normal and sham（ P 〈0. 01）,and the LID group＇s reduced more significantly than that of the PD group（ P 〈0. 01）,and the expression of p-GSK3β（ phospho S9） significantly decreased after treatment with Compound Formula Rehmannia（ P 〈0. 01）. Conclusion： CompoundFormula Rehmannia may alleviate the activation of GSK3β protein by regulating GSK3β signaling pathway,and then β-catenin phosphorylation would be weakened,free β-catenin would be transferred into the nucleus and α-syn would be activated,and so α-syn abnormal aggregation and error folding are limited and apoptosis is limited,thereby Parkinson＇s disease and dyskinesia were eased.

关 键 词：帕金森病 异动症 GSK-3β蛋白 复方地黄方 

分 类 号：R285.5[医药卫生—中药学]