硫辛酸对帕金森病小鼠模型自噬蛋白表达水平的影响

目的 探讨硫辛酸(lipoic acid,LA)对MPTP诱导的C57BL/6帕金森病(Parkinson's disease,PD)小鼠模型黑质及纹状体TH、parkin、PINK1、DJ-1自噬相关蛋白表达水平的影响。方法 将60只C57BL/6小鼠随机分为PD模型组、正常组、治疗组、预保护组,采用背部皮下注射MPTP制作PD模型(每组各15只),行为学评价造模,Western Blotting法检测黑质、纹状体TH、parkin、PINK1、DJ-1蛋白的表达水平,免疫组化法观察黑质及纹状体阳性神经元数,免疫荧光检测PINK1的表达水平。结果(1)与正常组比较,PD模型组小鼠黑质、纹状体内TH、Parkin、PINK1、DJ-1的表达水平均明显降低(P<0.01);(2)与PD模型组比较,预保护组黑质、纹状体内TH、PINK1、Parkin、DJ-1表达水平均明显增高(P<0.05);(3)与治疗组比较,预保护组小鼠黑质、纹状体内TH、PINK1、Parkin表达水平略增高,预保护组DJ-1表达水平略降低,但两组比较无统计学差异(P>0.05)。结论 线粒体自噬参与PD小鼠的发病过程; 硫辛酸可能通过上调PD小鼠自噬相关蛋白的表达水平而发挥对多巴胺神经元的保护作用,从而为PD的防治提供新的思路。

The effects of lipoic acid on autophagy protein expression levels in mouse model of Parkinson's disease

ObjectiveTo investigate the effects of lipoic acid(LA)on the expression levels of autophagy-related proteins(the substantia nigra and striatum TH, parkin, PINK1, DJ-1)in MPTP-induced C57BL/6 Parkinson's disease(PD)mouse model.Methods Sixty C57BL/6 mice were randomly divided into PD model group, normal group, treatment group and pre-protection group. PD model was made by subcutaneous injection of MPTP in the back(15 in each group). After behavioral evaluation model, Western Blotting method was used to detect the expression levels of nigrostria, striatum TH, parkin, PINK1, DJ-1 protein. The number of nigral and striatum-positive neurons was observed by immunohistochemistry. The expression level of PINK1 was detected by immunofluorescence.Results(1)Compared with the normal group, the expression levels of TH, PINK1 and DJ-1 in the substantia nigra and striatum of the PD model group were significantly decreased(P<0.05), and Parkin expression level was significantly increased in the PD model group(P<0.05).(2)Compared with the PD model group, the expression levels of TH, PINK1 and DJ-1 in the substantia nigra and striatum of the pre-protection group and the treatment group were significantly increased(P<0.05), and the Parkin protein expression level was significantly decreased(P<0.05).(3)Compared with the treatment group, the expression levels of TH, PINK1 and DJ-1 in the substantia nigra and striatum of the pre-protected group were slightly increased, and the expression level of Parkin was slightly decreased, but there was no significant difference between them(P>0.05).Conclusion Autophagy in nigrostigmata and spleen was inhibited in PD mouse model. Lipoic acid might play a role in the neuroprotective effect of Parkinson's disease by affecting the expression levels of autophagy-related proteins in PD mice, provide new ideas for the treatment of PD.