Ifenprodil对自噬的调控机制及其在帕金森病中的作用  

Mechanism of Ifenprodil Treatment in Autophagy Regulation and Effect on Parkinson′s Disease

作　　者：赵昕昱 田付港 于昕[1] ZHAO Xin-yu;TIAN Fu-gang;YU Xin(School of Pharmacy,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shan-dong,Yantai University,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Yantai 264005,China)

机构地区：[1]烟台大学药学院,烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心,分子药理和药物评价教育部重点实验室(烟台大学),山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2021年第3期315-322,共8页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：泰山学者项目(主持人:赵克浩)。

摘　　要：为探讨Ifenprodil在帕金森病(Parkinsan′s disease,PD)中自噬抑制的缓解作用,采用体内和体外两部分实验对其机制进行研究。对6-OHDA-PD大鼠模型进行随机分组给药,通过旋转试验和圆筒实验观察Ifenprodil对PD大鼠行为学改善作用,免疫组织化学法(IHC)检测中脑黑质TH阳性细胞的表达情况;采用不同浓度的Ifenprodil对谷氨酸诱导的SH-SY5Y细胞兴奋性神经毒模型进行治疗,MTT法检测细胞存活率,Western Blot法检测膜受体NR2B和NR2A,自噬蛋白lc3b、beclin-1和p62,凋亡相关蛋白bax和bcl-2的表达水平。结果显示,Ifenprodil可改善APO诱发的异常旋转行为,对黑质多巴胺神经元具有较好的保护作用,可在动物及细胞水平上调lc3b,beclin-1,bcl-2的表达,下调p62,bax的表达。结果提示,Ifenprodil对多巴胺神经元有较好的保护作用,其机制可能与调节NMDA受体亚基的表达,增强细胞自身的自噬作用相关。To investigate the remission effect of Ifenprodil on autophagy inhibition in Parkinson's disease(PD),in vivo and in vitro experiments are conducted.The 6-OHDA-PD rat models are randomly divided into different groups and administered.The behavioral improvement effect of Ifenprodil on PD rats is observed by rotation test and cylinder test,and immunohistochemistry(IHC)is used to detect the expression of TH positive cells in substantia nigra.Ifenprodil with different concentrations is used to treat SH-SY5Y cells with glutamate-induced excitatory neurotoxicity.MTT assay is used to detect cell survival rate.Western Blot is used to detect the expression levels of membrane receptors NR2B and NR2A,autophagy proteins lc3b,beclin-1 and p62,apoptosis-related proteins bax and bcl-2.The results show that Ifenprodil can improve the abnormal rotation induced by APO,protect dopaminergic neurons in substantia nigra,up-regulate the expression of lc3b,beclin-1 and bcl-2,and down-regulate the expression of p62 and bax at animal and cell levels,suggesting that Ifenprodil has a good protective effect on dopaminergic neurons,of which mechanism may be related to regulating the expression of NMDA receptor subunits and enhancing the autophagy of cells themselves.

关 键 词：帕金森病 IFENPRODIL 自噬 NMDA 

分 类 号：R964[医药卫生—药理学]