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rn目的探讨雷帕霉素对帕金森病(PD)大鼠模型的保护作用及其机制。方法 60只大鼠均分为5组:C组作为空白对照;其余4组采用6-羟基多巴(6-OHDA)两点注射法制备PD大鼠模型。LR、MR和HR组造模前7d开始用雷帕霉素0.05、0.5和5mg/kg每天灌胃给药1次;P组给予生理盐水作为模型对照。术后3周对大鼠进行行为学评分;检测纹状体丙二醛(MDA)和谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性,以及B细胞淋巴瘤/白血病2(Bcl-2)、Bcl-2相关X蛋白(Bax)和还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶p47phox mRNA的表达水平。结果与P组相比,LR、MR和HR组大鼠旋转圈数减少、纹状体MDA含量降低、GSH含量、SOD、GSH-PX活性以及Bcl-2mRNA表达升高、Bax和p47phox mRNA表达水平降低。结论雷帕霉素可以有效改善PD大鼠模型行为学表现。其机制可能与调控病灶相关部位的氧化应激水平及线粒体相关基因mRNA的表达有关。“,”Objective To investigate the protective effect of rapamycin on the rat model of Parkinson′s disease(PD) and its underlying mechanism.Methods Sixty SD rats were equally randomized into 5 groups.The rats in group C were taken as blank controls.PD model was produced with a unilateral injection of 6-hydroxydopamine into two different sites within the striatum in the other 4 groups.Rapamycin 0.05(group LR),0.5(group MR) or 5 mg/kg(group HR) was administered by gastric gavage once a day,starting on the 7th day prior to 6-OHDA injection.The rats in group P were injected normal saline as model controls.All rats were subjected to rotational behavior testing three weeks after surgery.The contents of MDA and GSH,activities of SOD and GSH-PX in the striatum were measured by assay kits.The mRNA expressions of Bax,Bcl-2 and p47phox in the striatum were analyzed by RT-PCR as well.Results Compared to group P,the cycles of rotation during rotational behavior testing were less,MDA level was reduced,content of GSH was increased,activities of SOD and GSH-PX were inceased,Bcl-2 mRNA expression was increased,and the expressions of Bcl-2 and p47phox were decreased in groups of LR,MR and HR.ConclusionRapamycin can improve the severity of PD rats,which may be related to the regulation of the status of oxidative stress and the level of mitodrondria-related gene mRNA expression in the lesion.