人参皂苷Rg1对帕金森病模型小鼠黑质区FADD和FLIP表达的影响及其意义

doi:10.13481/j.1671-587x.20140511

吉林大学学报(医学版)

人参皂苷Rg1对帕金森病模型小鼠黑质区FADD和FLIP表达的影响及其意义

王茜¹，张辉²，刘名³，李琪佳⁴，耿丽鑫⁴，孙明宏²，田清友¹，张宇新¹

（1.河北联合大学基础医学院人体解剖学系,河北唐山 063000；2.河北省唐山市第二医院关节病科,河北唐山 063000；3.河北省唐山市协和医院骨科，河北唐山 063004；4.河北联合大学医学中心实验室，河北唐山 063000）

收稿日期:2013-12-17 出版日期:2014-09-28 发布日期:2014-09-28
通讯作者: 张宇新 E-mail: (Tel:0315-3726421， E-mail:jpzyx@163.com)
作者简介:王茜(1981-)，女，河北省衡水市人，讲师，在读医学博士,主要从事人体解剖学、神经解剖和医学移植材料等方面研究。
基金资助:
河北省科技厅自然科学基金资助课题（C2004000689）;河北省博士基金资助课题（05547008D-4）;河北省科学技术与社会发展计划项目资助课题（04276135）;河北省唐山市科技局科学技术研究与发展指令计划性项目资助课题（13130267z）;河北联合大学科学研究基金资助课题（Z201236）;河北联合大学大学生创新性实验计划资助课题(X2013034);河北省教育厅大学生创新创业训练计划项目资助课题（201310081023）

Influence of ginsenoside Rg1 in expressions of FADD and FLIP in substantia nigra of Parkinson’s disease model mice

WANG Qian¹,ZHANG Hui²,LIU Ming³,LI Qi-jia⁴,GENG Li-xin⁴,SUN Ming-hong²,TIAN Qing-you¹,ZHANG Yu-xin¹

(1. Department of Anatomy,College of Basic Medical Science,Hebei United University,Tangshan 063000,China;2. Department of Joint Surgery,Second Hospital of Tangshan City,Hebei Province,Tangshan 063000,China;3. Department of Orthopedics,Xiehe Hospital of Tangshan City,Hebei Province,Tangshan 063004,China;4.Medical Experiment Center,Hebei United University,Tangshan 063000,China)

Received:2013-12-17 Online:2014-09-28 Published:2014-09-28

摘要/Abstract

摘要：

目的：探讨人参皂苷Rg1对帕金森病（PD）模型小鼠黑质区凋亡信号蛋白Fas死亡结构域蛋白(FADD)、FADD样白细胞介素1-转化酶样抑制蛋白(FLIP)及Caspase-3表达的影响，阐明FADD和FLIP在PD发病机制中的作用及人参皂苷Rg1对多巴胺（DA）能神经元的保护作用。方法： 45只C57BL/6N小鼠随机分为对照组、模型组和人参皂苷Rg1组，每组15只。模型组小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP)，人参皂苷Rg1组小鼠注射MPTP前先注射人参皂苷Rg1，对照组小鼠腹腔注射生理盐水。观察各组小鼠行为学变化；采用免疫组织化学法和免疫蛋白印迹法检测各组小鼠中脑黑质区酪氨酸羟化酶（TH）、FLIP、FADD及Caspase-3的表达。结果：与对照组比较，模型组小鼠出现典型PD症状，黑质区TH阳性细胞数明显减少(P<0.01)，FADD、FLIP及Caspase-3阳性细胞数明显增加(P<0.01)，胞浆染色深；FADD、FLIP及Caspase-3蛋白表达水平升高(P<0.01)。与模型组比较，人参皂苷Rg1组小鼠PD症状减轻，黑质区TH阳性细胞数明显增多(P<0.01)，FADD、FLIP及Caspase-3阳性细胞数明显减少(P<0.01)，胞浆染色浅；FADD、FLIP和Caspase-3蛋白表达水平降低 (P<0.01)。FADD与Caspase-3阳性细胞数呈正相关关系(r= 0.791,P< 0.05)。结论：人参皂苷Rg1可通过影响PD模型小鼠黑质区FADD和FLIP的表达对DA能神经元起到一定的保护作用。

关键词: 帕金森病, Fas死亡结构域蛋白, FADD样白细胞介素1-转化酶样抑制蛋白, 半胱氨酸蛋白酶-3, 人参皂苷Rg1

Abstract:

Abstract:Objective
To investegate the effect of ginsenoside Rg1 on the apoptosis related protein FLICE- inhibitory protein(FLIP),Fas-associated death domain protein (FADD) and Caspase-3 in the subatania nigra(SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahyd- ropyridine (MPTP)-induced mouse models of Parkinson’s disease(PD),and to investigate the role of FADD and FLIP in the pathogenesis of PD and the protective effect of ginsenosides Rg1 on dopaminergic neurons.Methods 45 C57BL/6N mice were randomly divided into control group, model group and ginsenoside Rg1 group (n=15).The mice in model group were injected with MPTP by intraperitoneal,the mice in Rg1 group were injected with ginsenoside Rg1 before injecting MPTP,and the mice in control group were injected with normal saline by intraperitoneal.The behavioral changes of the mice in various groups were observed,and immunohistochemistry and Western blotting methods were used to observe the expressions of tyrosine hydroxylase(TH),FADD,FLIP and Caspase-3 in substantia nigra of the mice.Results Compared with control group,the mice in model group presented with typical symptoms of PD,the TH-positive neurons in the subatania nigra was significantly reduced (P<0.01),the number of FADD,FLIP and Caspase-3 positive cells was significantly increased(P<0.01),and the cytoplasm was deeply stained;the protein expression levels of FADD,FLIP and Caspase-3 were significantly increased (P<0.01).Compared with model group,the PD symptoms of the mice in ginsenoside Rg1 group reduced,the number of TH-positive neurons was significantly increased,the number of positive cells of FLIP,FADD and Caspase-3 were significantly reduced(P<0.01),and the cytoplasm was lightly stained;the protein expression levels of FADD,FLIP and Caspase-3 were significantly reduced (P<0.01).Nonlinear correlation analysis found that there was a positive relationship between the number of FADD and Caspase-3 positive cells (r=0.791,P<0.05).Conclusion Ginsenoside Rg1 may play a neural protective effect dopaminergic on neurons by modulating the FADD and FLIP expressions in SN of PD model mice.

Key words: Parkinson&rsquo, s disease, Fas-associated death domain, FLICE- inhibitory proteins, caspase-3, ginsenoside Rg1

中图分类号:

王茜，张辉，刘名，李琪佳，耿丽鑫，孙明宏，田清友，张宇新. 人参皂苷Rg1对帕金森病模型小鼠黑质区FADD和FLIP表达的影响及其意义[J]. 吉林大学学报(医学版), 2014, 40(05): 962-966.

WANG Qian,ZHANG Hui,LIU Ming,LI Qi-jia,GENG Li-xin,SUN Ming-hong,TIAN Qing-you,ZHANG Yu-xin. Influence of ginsenoside Rg1 in expressions of FADD and FLIP in substantia nigra of Parkinson’s disease model mice[J]. Journal of Jilin University Medicine Edition, 2014, 40(05): 962-966.

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人参皂苷Rg1对帕金森病模型小鼠黑质区FADD和FLIP表达的影响及其意义

Influence of ginsenoside Rg1 in expressions of FADD and FLIP in substantia nigra of Parkinson’s disease model mice

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