表没食儿茶素没食子酸酯对帕金森病大鼠的神经保护作用及其机制探讨

目的观察表没食儿茶素没食子酸酯（epigallocatechin-3-gallate，EGCG）对鱼藤酮致帕金森（Parkinson disease，PD）大鼠模型黑质多巴胺能神经元的保护作用。方法健康成年雄性Wistar大鼠60只，随机分为对照组、实验组和药物干预组（每组20只）。实验组和药物干预组背部皮下注射鱼藤酮制备PD大鼠模型，药物干预组同时给予大鼠腹腔注射EGCG。采用分光光度法检测大鼠脑内丙二醛（malondialdehyde，MDA）和还原型谷胱甘肽（dutathione，GSH），免疫组织化学和Western blot检测大鼠中脑黑质及纹状体中酪氨酸羟化酶（tyrosine hydroxylase，TH）的表达变化。结果实验组大鼠纹状体中MDA明显增高（P〈0．05），GSH含量明显降低（P〈0．05），中脑TH免疫反应阳性神经元数明显少于对照组（P〈0．05），TH蛋自在黑质和纹状体与对照组比较明显降低（P〈0．05）；EGCG干预后与实验组相比MDA明显降低及GSH明显增高（P〈0．05），TH免疫反应阳性神经元数明显增加（P〈0．05），TH蛋白明显增加（P〈0．05）。结论化应激在PD发病中起着非常重要的作用，抗氧化治疗能有效减轻大鼠脑内多巴胺能神经元损伤情况，同时改善PD样症状，为PD的治疗提供了新的靶点。

MECHANISM OF EPIGALLOCATECHIN-3-GALLATE NEUROPROTECTION IN PARKINSON DISEASE RATS INDUCED BY ROTENONE

Objective To investigate the protective effect of epigallocatechin-3-gallate（EGCG） on the substantia nigra dopaminergic neuron in Parkinson disease （PD） rats induced by rotenone. Methods The healthy adult male 60 Wistar rats were randomly distributed to the following groups： control group, PD group and drug therapy group （n =20 each group）, PD and drug therapy groups were injected subcutaneously rotenone in the back to prepare the PD rats model, the rats of drug therapy group were injected intraperitoneally EGCG at the same time. Spectrophotometry was used to detect oxidative stress parameters in rats （malondialdehyde and glutathione）, immunocytochemistry and western blot were used to detect the expression of tyrosine hydroxylase （TH） in the substantia nigra and striatum of rats. Results Malondialdehyde （MDA） was significantly higher （ P 〈 0.05 ）, and glutathione （GSH） was significantly decreased （P 〈 0.05 ） in the rats striatum of rotenone group than those of control group. The number of TH positive neurons in midbrain was significantly less than that of control group （P 〈 0.05 ）, but the expression of TH was significantly decreased in the substantia nigra and striatum compared with control group （P 〈 0. 05 ）; MDA obviously docreased and GSH increased significantly after the intervention of EGCG compared with that of rotenone group （ P 〈 0.05 ）, the number of TH positive neurons significantly increased （P 〈 0. 05 ） and TH protein increased significantly （P 〈 0. 05 ）. Conclusion Oxidative stress plays a very important role in the pathogenesis of PD, anti-oxidation treatment can effectively reduce the injury of dopaminergic neurons in the brain of rat, which provides a new target for the treatment of PD.