咪多吡对帕金森病模型大鼠黑质纹状体自噬及自噬相关蛋白表达的影响  

Effects of Eldepryl on autophagy and autophagy-related protein in substantia nigra and striatum in rats with Parkinson's disease

作　　者：刘斌[1] 孙静[1] 张晋霞[1] 马原源[1] 毛文静[1] 吕超男[1] 成晓华 李世英[1] 

机构地区：[1]河北联合大学附属医院神经内一科,唐山063000

出　　处：《中国神经精神疾病杂志》2014年第9期522-526,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：河北省医学科学研究重点课题(编号:20130064)

摘　　要：目的观察咪多吡对帕金森病(Parkinson disease,PD)模型大鼠黑质纹状体自噬及自噬相关蛋白Beclin1和微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,MAPl LC3,简称LC3)的表达的影响,探讨咪多吡治疗帕金森病的作用机制。方法 72只健康SD大鼠随机分为假手术组(n=24)、帕金森病模型组(模型组n=24)和咪多吡治疗组(咪多吡组n=24),每组又分为模型制备后4 d、8 d两个亚组(每个亚组n=12)。采用颈背部皮下注射鱼藤酮制作帕金森病模型,免疫组化法和Western blotting法检测黑质纹状体自噬相关蛋白Beclin1和LC3的表达水平。结果与假手术组比较,模型组大鼠黑质纹状体中Beclin1、LC3蛋白表达和LC3II/LC3I比值增多(均P<0.05),8 d组高于4 d组(均P<0.05)。与模型组比较,咪多吡组黑质纹状体中Beclin1、LC3蛋白表达和LC3II/LC3I比值降低(均P<0.01),8 d组低于4 d组(均P<0.05)。结论咪多吡可能通过抑制大鼠PD模型黑质纹状体神经细胞自噬,发挥对帕金森病的治疗作用。Objective To examine the effects of eldepryl on autophagy and autophagy-related proteins such as Beclinl and LC3 in the substantia nigra and striatum in a rat model of Parkinson disease （PD）. Methods A total of 72 SD rats were randomly divided into sham-operated group （n=24）, PD model group （n=24）and Eldepryl treatment group （n= 24）. Each group was further divided into 4 d and 8 d subgroups following the establishment of PD model. The model of PD was established by subcutaneous injection of rotenone in rats. The expression of Beclinland LC3 in the substantia nigra and striatum was detected by using immunohistochemistry and western blotting. Results The expression levels of Beclinl, LC3 and LC3II/LC3I in the substantia nigra and striatum were increased in the model group than in the sham operation group （all P 〈0.05）. The increase in expression of Beclinl,LC3 and LC3II/LC3I was more obvious at 8 d than at 4 d group （all P 〈0.05）. The expression levels of Beclinl, LC3 and LC3II/LC3I in the substantia nigra and striatum were reduced in the eldepryl treatment group than in the model group （all P〈0.01）. The expression levels of Beclinl, LC3 and LC3II/LC31 were significantly lower at 8 d than at 4 d groups （all P 〈0.05） in eldepryl treatment group. Conclusions E1- depryl can protect against PD through inhibition of autophagy in the substantia nigra and striatum in rats.

关 键 词：帕金森病 咪多吡 自噬 LC3 BECLIN1 

分 类 号：R742.5[医药卫生—神经病学与精神病学]