【摘要】 目的:研究依达拉奉及帕吉林对鱼藤酮诱导的帕金森病(PD)大鼠模型的保护作用及机制。方法:60只5周龄♂Wistar大鼠随机分为4组,即鱼藤酮处理组、依达拉奉组、帕吉林组及对照组。分别给予鱼藤酮、鱼藤酮+依达拉奉、鱼藤酮+帕吉林和大豆油连续皮下注射8周。造模结束后处死动物游离中脑,进行免疫组织化学分析及电镜观察,并用流式细胞仪检测细胞内活性氧簇(ROS)的变化及线粒体膜电位改变。结果:相对于对照组,鱼藤酮组大鼠中脑神经元内ROS表达上升、线粒体膜电位严重降低(P<0.01);依达拉奉处理可以减缓鱼藤酮诱导的ROS的产生及线粒体膜电位的下降,并上调抗凋亡蛋白Bcl-2、Bcl-XL的表达,动物也未出现明显的PD症状;帕吉林组大鼠中脑神经元内ROS产生仍较高,虽然线粒体膜电位下降有所缓解,但大鼠仍表现出PD的行为学特征。结论:依达拉奉可能通过减少鱼藤酮诱导的ROS产生而对PD大鼠发挥神经保护作用。而帕吉林的保护作用并不明显,虽然可部分减少中脑神经元线粒体膜电位的下降,但仍不足以防止PD症状的出现。更多还原

【Abstract】 OBJECTIVE To investigate the effects of edaravone and pargyline on rotenone induced PD rats.METHODS 60 male Wistar rats were randomly divided into 4 groups: Rotenone group received rotenone mixed with soya bean oil only(2 mg·kg·d-1,subcutaneously);Edaravone group received rotenone and edaravone(10 mg·kg·d-1,intraperitoneally);Pargyline group received rotenone and pargyline(10 mg·kg·d-1,intraperitoneally);and control group received soya bean oil only(1 mL·kg·d-1,subcutaneouly).The animals were treated for 8 weeks.Bcl-2,Bcl-XL and Bax expressions were detected using immunohistochemical methods;Oxidative stress and mitochondrial membrane potential in midbrain neurons was determined by FACS using Carboxy-H2DCFDA and JC-1 stain respectively.RESULTS Chronic administration of rotenone does cause PD in rats.Compared with control group,ROS in the midbrain of rotenone group increased but mitochondrial membrane potential decreased(P<0.01);Edaravone group had a much lower ROS expression and higher mitochondrial membrane potential compared with Rotenone group(P<0.01).The expression of anti-apoptotic protein Bcl-2、Bcl-XL is up-regulated and no PD signs appeared in edaravone group as well.Pargyline group has similarly results with rotenone group.CONCLUSION Edaravone provided protection against rotenone induced PD rats.But our data didn’t show a substantial protective effect of pargyline.更多还原