罗格列酮通过抗凋亡机制保护帕金森病模型小鼠多巴胺神经元  

Rosiglitazone protects dopaminergic neurons in the mouse model of Parkinson's disease from apoptotic cell death

作　　者：张田[1] 秦丽娟[1] 魏子峰[2] 周洪霞[2] 李树民[1] 张宇新[2] 

机构地区：[1]河北联合大学基础医学院生理学系,河北唐山063000 [2]河北联合大学基础医学院解剖学系,河北唐山063000

出　　处：《中风与神经疾病杂志》2014年第5期401-404,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究罗格列酮在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中对多巴胺能神经元的保护作用。方法采用MPTP制备PD小鼠模型,观察各组小鼠行为学变化,免疫组织化学和免疫印迹法观察中脑黑质TH、caspase-9、caspase-6、Bcl-2和Bax的表达变化,TUNEL检测细胞凋亡情况,并观察给予罗格列酮后对上述变化的影响。结果模型组小鼠出现竖毛、翘尾、震颤、肌肉强直和运动变缓等PD样症状,黑质区TH阳性神经元缺失,并伴有Caspase-9、caspase-6、Bax高表达及TUNEL阳性细胞增加,而Bcl-2的表达与对照组相比下降;经罗格列酮处理后,上述情况得到一定程度逆转。结论罗格列酮可通过阻抑凋亡调控蛋白的异常表达,发挥对PD模型小鼠多巴胺能神经元保护作用。Objective To investigate the protective effect of Rosiglitazone on the dopaminergic neurons in the substania nigra（ SN） in MPTP-induced mouse model of Parkinson＇s disease（ PD）. Methods C57BL /6N mice were administrated with MPTP to produce subacute PD model. The behavioral changes of different groups were observed,Apoptotic cell number were determined byTdT-mediated dUTP-biotin nick end labeling（ TUNEL）,immunohistochemistry and western blot methods were used to investigate the positive cell numbers and the protein expression of TH,caspase-9,caspase-6,Bcl-2 and Bax. The above changes,after giving Rosiglitazone,were also studied. Results The model mice exhibited typical PD-like behaviors,such as tremor,myotonia,and dyskinesia. The TH-positive neurons lost markedly,the expression level of TUNEL,caspase-9,caspase-6,and Bax in SN of the midbrain increased markedly. But the expression level of Bcl-2 decreased. After giving Rosiglitazone,the above changes reduced obviously. Conclusions Rosiglitazone may protect the dopaminergic neurons through its potent antiapoptotic properties.

关 键 词：帕金森病 酪氨酸羟化酶 细胞凋亡 罗格列酮 

分 类 号：R742.5[医药卫生—神经病学与精神病学]