Jin Feng, Wu Qin, Lu Yuan-Fu, Gong Qi-Hai, Shi Jing-Shan
Department of Pharmacology, Zunyi Medical College, Zunyi, PR China.
Eur J Pharmacol. 2008 Dec 14;600(1-3):78-82. doi: 10.1016/j.ejphar.2008.10.005. Epub 2008 Oct 10.
The present study was undertaken to investigate the neuroprotective effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. 6-OHDA-induced Parkinson's disease rat model involves chronic inflammation, mitochondrial dysfunction, and oxidative stress, and the loss of the dopaminergic neurons in the substantia nigra is the predominant lesion. Resveratrol has been shown to have anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced Parkinson's disease rat model. Adult Sprague-Dawley (SD) rats were unilaterally injected with 6-OHDA (5 microg/2 microl) into the right striatum, and the striatum damage was assessed by rotational test, ultrahistopathology, and molecular alterations. Resveratrol (10, 20 and 40 mg/kg) was then given orally to Parkinson's disease rats, daily for 10 weeks to examine the protective effects. Rotational test (turns of rats) showed that resveratrol significantly attenuated apomorphine-induced turns of rats in 6-OHDA-injuried Parkinson's disease rat model as early as two weeks of administration. Ultrastructural analysis showed that resveratrol alleviated 6-OHDA-induced chromatin condensation, mitochondrial tumefaction and vacuolization of dopaminergic neurons in rat substantia nigra. Furthermore, resveratrol treatment also significantly decreased the levels of COX-2 and TNF-alpha mRNA in the substantia nigra as detected by real-time RT-PCR. COX-2 protein expression in the substantia nigra was also decreased as evidenced by Western blotting. These results demonstrate that resveratrol exerts a neuroprotective effect on 6-OHDA-induced Parkinson's disease rat model, and this protection is related to the reduced inflammatory reaction.
本研究旨在探讨白藜芦醇对6-羟基多巴胺（6-OHDA）诱导的大鼠帕金森病的神经保护作用。6-OHDA诱导的帕金森病大鼠模型涉及慢性炎症、线粒体功能障碍和氧化应激，黑质中多巴胺能神经元的丧失是主要病变。白藜芦醇已被证明具有抗炎作用，因此使用6-OHDA诱导的帕金森病大鼠模型测试其有益效果。将成年Sprague-Dawley（SD）大鼠右侧纹状体单侧注射6-OHDA（5微克/2微升），并通过旋转试验、超微组织病理学和分子改变评估纹状体损伤。然后给帕金森病大鼠口服白藜芦醇（10、20和40毫克/千克），每天一次，持续10周，以检查其保护作用。旋转试验（大鼠旋转次数）表明，早在给药两周时，白藜芦醇就显著减轻了6-OHDA损伤的帕金森病大鼠模型中阿扑吗啡诱导的大鼠旋转次数。超微结构分析表明，白藜芦醇减轻了6-OHDA诱导的大鼠黑质中多巴胺能神经元的染色质浓缩、线粒体肿胀和空泡化。此外，实时RT-PCR检测显示，白藜芦醇治疗还显著降低了黑质中COX-2和TNF-α mRNA的水平。蛋白质印迹法证实，黑质中COX-2蛋白表达也降低。这些结果表明，白藜芦醇对6-OHDA诱导的帕金森病大鼠模型具有神经保护作用，且这种保护作用与炎症反应减轻有关。
