ATP敏感性钾通道亚基Kir6．1、Kir6．2在MPTP诱导帕金森病小鼠纹状体和黑质内的改变  

Expression alterations of the Kir6.1, Kir6.2 subunits of ATP-sensitive potassium channels in the striatum and substantia nigra of MPTP-induced parkinsonian mice

作　　者：王刚[1] 潘静[1] 曾洁[1] 任汝静[1] 陈生弟[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院神经科,上海交通大学医学院神经病学研究所,上海200025

出　　处：《神经解剖学杂志》2008年第1期13-18,共6页Chinese Journal of Neuroanatomy

基　　金：上海市高校选拔培养优秀青年教师科研专项基金(18015);国家自然科学基金(No30700251);国家重点基础研究规划(2006cb500700)资助项目

摘　　要：为探讨ATP敏感性钾通道(KATP)亚基Kir6.1、Kir6.2在帕金森病(PD)病理生理机制中的可能作用。本研究采用蛋白免疫印迹分析(Western blot)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的PD小鼠模型黑质、纹状体Kir6.1、Kir6.2在不同时间点表达变化进行检测,并与酪氨酸羟化酶(TH)的变化进行比较。结果发现:(1)与正常对照组相比,黑质、纹状体TH蛋白的表达在给药后第1d即开始下降,且呈时间依赖性下降(P<0.01);(2)黑质Kir6.1蛋白的表达在给药后第5d才开始下降(P<0.01);而纹状体Kir6.1蛋白的表达在给药后第5d才开始升高(P<0.01);(3)黑质Kir6.2蛋白的表达在给药后第5d才开始明显升高(P<0.01);而纹状体Kir6.2蛋白的表达在给药后第3d轻度升高(P<0.05),第5d又明显降低(P<0.01)。以上结果提示作为KATP通道亚基的Kir6.1、Kir6.2在MPTP的作用下,可能通过参与星形胶质细胞的活化、胆碱能突触传递的抑制以及自身代偿和修复在PD的病理生理过程中发挥了重要的角色。To investigate the roles of Kit6, 1 and Kit6.2 subunits in the pathological mechanism of Parkinson＇s disease （PD）. Western blot was used to detect the alterations of Kit6 proteins in different time courses （0, 1,3 and 5 days after 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） injections） at different structures of brain （ the striatum and substantia nigra） in parkinsonian mice. The alterations of the Kit6 proteins were also compared with those of tyrosine hydroxylase （TH）. The results demonstrated that （ 1 ） the expression of TH protein was declined in a dose-dependent manner （ P 〈 0.01 ） one day after MPTP treatment ; （2） the expression of Kit6.1 protein was decreased in the substantia nigra but increased in the striatum at day 5 after MPTP treatment （ P 〈 0.01 ） ; （ 3 ） the expression of Kit6.2 protein began to increase in the substantia nigra at day 5 after MPTP infusion （ P 〈0.01 ）, starting to enhance in the striatum at day 3 after MPTP administration （ P 〈 0.05 ）, while beginning to decline at day 5 following MPTP insult （ P 〈 0.01 ）. It is concluded that the alterations of Kit6 proteins are delayed compared with the TH in MPTP-intoxicated mice, and MPTP oppositely alters the expression of Kit6 protein. Kit6 subunits are involved in the pathophysiology of PD via activating the astrocytes, inhibiting the cholinergic making self-reparation.

关 键 词：ATP敏感性钾通道 蛋白免疫印迹 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]