罗格列酮对帕金森病模型小鼠炎症反应和细胞凋亡的影响

摘要

目的：观察炎症反应和细胞凋亡在帕金森病发病过程中的作用，探讨罗格列酮对PD多巴胺（ DA）能神经元的保护作用。方法采用1-甲基-4-苯基-1，2，3，6四氢吡啶（MPTP）制备PD模型，观察各组小鼠行为学变化，免疫组织化学和免疫印迹观察小鼠中脑黑质酪氨酸羟化酶（TH）、环氧合酶（COX）-2、前列腺素E2（PGE2）和半胱氨酸蛋白酶（caspase）-3的表达变化，及给予罗格列酮后对上述变化的影响。结果模型组小鼠出现震颤、步态迟缓等PD 样症状，黑质区TH阳性神经元缺失，COX -2、PGE2和caspase-3阳性细胞明显增多，蛋白水平亦升高；经罗格列酮治疗后，上述症状得到改善。结论罗格列酮对PD小鼠DA能神经元保护作用可能与抑制炎症反应和细胞凋亡有关。%Objective To investigate the effects of inflammatory response and apoptosis during the pathogenetic process of Parkin -son′s disease (PD) and explore the protective effect of Rosiglitazone on dopaminergic neurons in PD.Methods C57BL/6N mice were ad-ministrated with MPTP to produce subacute PD model.The behavioral changes of different groups were observed , immunohistochemistry and Western blot methods were used to investigate the positive cell numbers and the protein expression of COX -2, PGE2, caspase-3 and TH.The above changes , after giving Rosiglitazone , were also studied.Results The model mice exhibited typical PD-like behaviors , TH-positive neurons lost markedly , the number of COX-2, PGE2, caspase-3 and TH immunoreactive cells and their expression level in SN of the mid-brain increased markedly.After giving Rosiglitazone , the above changes were reduced obviously.Conclusions The neuroprotective effect of Rosiglitazone on the dopaminergic neurons may inhibit the inflammatory response and apoptosis .