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

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。

Expression alterations of the Kir5.1.Kir6.2 subunits of ATP-sensitive potassium channels in the striatum and substantia nigra of MPTP-induced parkinsonian mice

To investigate the roles of Kir6.1 and Kir6.2 subunits in the pathological mechanism of Parkinson’s disease (PD). Western blot was used to detect the alterations of Kir6 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 Kir6 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 Kir6.1 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 Kir6.2 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 Kir6 proteins are delayed compared with the TH in MPTP-intoxicated mice, and MPTP oppositely alters the expression of Kir6 protein. Kir6 subunits are involved in the pathophysiology of PD via activating the astrocytes, inhibiting the cholinergic neurotransmission and making self-reparation.