6-羟基多巴在帕金森病发病机制中的作用

目的：探讨神经毒素6-羟基多巴（6-OHDA）在帕金森病（PD）发病机制中的作用。 方法：采用立体定向术将神经毒素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。造模2个月后，检测其纹状体内还原型谷胱甘肽(GSH)和活性氧，并观察黑质的病理改变。结果：帕金森病模型组右侧纹状体内GSH含量［（36.85±8.64 μg•mg^-1 prot）］明显下降，活性氧含量［（58.69±9.84）U•mg^-1 prot］明显增高，与假手术组及正常对照组比较差异均有显著性（P<0.05）。光镜下可见帕金森病模型组右侧黑质致密带内多巴胺能神经元减少，与模型组左侧及对照组、假手术组黑质相比差异均有显著性（P<0.05）。 结论：6-OHDA可通过耗竭GSH及增加自由基的生成损害多巴胺能神经末梢，并逆行性损毁神经元胞体，导致黑质致密带多巴胺能神经元变性死亡。

Role of 6-hydroxydopamine in pathogenesis of Parkinson's disease

Objective To explore the role of 6-hydroxydopamine in the pathogenesis of Parkinson′s disease(PD). Methods The 6-hydroxydopamine(6-OHDA) was stereotaxically injected into the right striatum of rat to build the PD model. After two months, the levels of glutathione (GSH) and reactive oxygen in the striatum were measured, and the pathological changes in the substantia nigra (SN) were observed. Results The level of GSH of right side of striatum in model groups (36.85±8.64 μg·mg -1 prot) decreased significantly and the level of reactive oxygen (58.69±9.84 U·mg -1 prot)increased markedly. There were significant differences between the right and left striatum in animal model groups (P<0.05). Compared with the sham group and control group, there were also significant differences (P<0.05). The dopaminergic neuron number in the right SN in model group decreased significantly compared with the left SN, sham group, and control group (P<0.05). Conclusion 6-OHDA can increase the level of free radicals and decrease the level of GSH, thus leading to the oxidative lesions in SN and striatum and neuronal death.