神经胶质细胞在帕金森病发病机制中的作用

The Role of gliacytes in the pathogenesis of Parkinson's disease

目的 探讨胶质细胞在帕金森病 ( Parkinson's disease,PD)发病机制中的作用。方法 采用立体定向术将神经毒素 6 -羟基多巴 ( 6 - hydroxydopamine,6 - OHDA)注入大鼠右侧纹状体内 ,制备经典的帕金森病动物模型。观察黑质致密带内多巴胺 ( dopamine,DA)能神经元缺失、胶质细胞的增生和肿瘤坏死因子 ( tumor necrosis factor-alpha,TNF- α)表达水平。结果 模型组右侧黑质 DA能神经元的数量明显减少 ,同时伴有星形胶质细胞和小胶质细胞的数量明显增高 ( P<0 .0 5 ) ,TNF- α在模型组右侧黑质和纹状体内有阳性表达 ,且主要分布在激活的小胶质细胞上。结论 神经胶质细胞可能是通过 TNF- α等细胞因子 ,导致或参与 DA能神经元的大量的变性、死亡。以抑制小胶质细胞的激活作为靶点的药物研究有可能为 PD的治疗提供新的思路。

Objective To explore the role of gliacytes in the pathogenesis of Parkinson's disease (PD) in the rat models of PD induced by 6-hydroxydopamine(6-OHDA).Methods The 6-OHDA was stereotaxically injected into the right striatum of rats at two sites to produce rat models of PD.Thenwe observed the loss of DA neurons,account the alteration in quantity of microglias and astrocytes by nigral hematoxylin & eosin (HE) stain and the expression of tumor necrosis factor-alpha (TNF-α) in the substantia nigra pars compacta and striatum by immunohistochemical stain under optical microscope.Statistical analysis were performed using Student's t-test.The P value less than 0.05 was regarded as statistically significant.Results The microgliocytes and astrocytes were increased in quantity in the right substantia nigra compacta of PD model group( P <0.05).TNF-α was positive expressed in the rightstriatum and right substantia nigra compacta of PD model group and distributed primarily on the activated microgliocytes.Conclusions Gliacytesparticipate the degeneration and death of neurons in the rat model of PD by TNF-α and other cytokines.So the reseach on drugs which can inhibit the activation of microglia cells may provide new methods for the treatment of PD.