松果菊苷对帕金森病模型大鼠纹状体GRP78及MANF表达的影响

Influences of Echinacoside on the Expression of GRP 78 and MANF in Striatum of Parkinson′s Disease Model Rats

目的观察松果菊苷对帕金森病模型大鼠纹状体葡萄糖调节蛋白78(GRP78)及中脑星形胶质细胞源性神经营养因子(MANF)蛋白含量的影响。方法 32只雄性SD大鼠随机分为正常组、溶剂组及造模组。连续颈背部皮下注射鱼藤酮葵花油乳化液14 d建立帕金森病大鼠模型,将造模成功的大鼠随机分为模型组与治疗组,每组8只。治疗组予以松果菊苷20 mg/(kg·d)灌胃。其余各组予以等量生理盐水灌胃,连续给药14 d。各组大鼠于松果菊苷治疗前1 d及治疗14 d后行悬挂试验;药物干预结束后,麻醉下处死大鼠取纹状体,蛋白质印迹法(Western Blot)检测GRP78及MANF蛋白的表达。结果治疗前1 d,模型组及治疗组大鼠悬挂时间较正常组缩短(P<0.01);治疗14 d后,治疗组大鼠悬挂时间较模型组延长(P<0.05)。与正常组比较,模型组GRP78蛋白表达增高,MANF蛋白表达降低(P<0.05);与模型组比较,治疗组GRP78蛋白表达降低,MANF蛋白表达升高(P<0.05)。结论松果菊苷可能通过调节内质网应激相关蛋白GRP78表达及增加MANF的表达改善帕金森病的行为障碍。

Objective To observe the effect of echinacoside on the contents of glucose-regulated protein78(GRP78) and mesencephalic astrocyte-derived neurotrophic factor(MANF) protein in striatum of Parkinson′s disease model rat.Methods Thirty-two male Sprague-Dawley rats were randomly divided into normal group,solvent group and rotenone group.Rat model of Parkinson′s disease was established by subcutaneous injection of rotenone sunflower oil emulsion for 14 days.The rats with successful modeling were randomly divided into model group and treatment group,with 8 rats in each group.The rats in treatment group were given intragastric administration of echinacoside 20 mg/(kg·d) for 14 days.The rats in each group underwent traction test 1 day before and after 14 days treatment with echinacoside. After the drug intervention,the rats were sacrificed under anesthesia for striatum,and the expression of GRP78 and MANF was detected by Western Blot.Results One day before treatment,the suspension time of the model group and treatment group was significantly shorter than that of the normal group(P<0.01).After 14 days of treatment,the suspension time of treatment group was significantly longer than that of the model group(P<0.05).Compared with the normal group,the expression of GRP78 protein in the model group was increased,MANF protein in the model group was decreased(P<0.01).Compared with the model group,the expression of GRP78 protein in the treatment group was decreased,MANF protein in the model group was increased(P<0.01).Conclusion Echinacoside may improve the expression of MANF and regulate the expression of endoplasmic reticulum stress-related protein GRP78 to alleviate the behavioral disorder of Parkinson′s disease.