【摘要】 目的 探讨二苯乙烯苷(TSG)对阿尔茨海默病(AD)小鼠细胞周期蛋白依赖性激酶(CDK)5、细胞外蛋白调节激酶(MAPK)1、蛋白磷酸酶(PP)1的调控作用。方法 淀粉样前体蛋白(APP)/早老蛋白(PS)1/Tau三转基因AD雄性小鼠45只，按体重随机分为5组，分别为模型组、阳性对照组(0.150 mg/kg石杉碱甲)、TSG低剂量组(0.033 g/kg TSG)、TSG中剂量组(0.100 g/kg TSG)、TSG高剂量组(0.300 g/kg TSG),再选取C57BL/6J雄性小鼠作为正常对照组，每天灌胃1次，连续给药60 d。采用免疫组织化学(IHC)染色法检测各组大脑皮层、海马P39蛋白表达水平；Western印迹检测各组脑组织CDK5、MAPK1及PP1蛋白表达水平；采用实时荧光定量-聚合酶链反应(qRT-PCR)检测各组CDK5、MAPK1及PP1 mRNA转录水平。结果 与正常对照组比较，其余各组海马区及大脑皮层P39平均光密度值和阳性神经元细胞总数目显著增多、CDK5和MAPK1 mRNA及蛋白表达水平显著增高，PP1 mRNA及蛋白表达水平显著降低(均P<0.05);与模型组比较，TSG各剂量组海马区及大脑皮层P39平均光密度值和阳性神经元细胞总数目显著降低，CDK5、MAPK1 mRNA及蛋白表达水平显著降低，PP1 mRNA及蛋白表达水平显著增高(均P<0.05)。结论 TSG对APP/PS1/Tau AD小鼠具备一定的改善作用，其机制可能与下调CDK5、MAPK1转录及表达、上调PP1转录及表达、抑制Tau蛋白磷酸化有关。更多还原

【Abstract】 Objective To investigate the regulatory effects of stilbene glycoside(TSG) on CDK5,MAPK1 and PP1 in Alzheimer′s disease mice.Methods Forty-five APP/PS1/Tau transgenic Alzheimer′s disease(AD) mice were randomly divided into 5 groups according to body weight, model group, positive control group(Huperzine A,0.150 mg/kg),TSG low dose group(0.033 g/kg),TSG medium dose group(0.100 g/kg),TSG high dose group(0.300 g/kg),C57 BL/6 J male mice were selected as normal control group.Drug was given once a day by gavage for consecutive 60 days.Immunohistochemical(IHC) staining method was used to detect the expression of P39 in each group mice cortex and hippocampus; Western blotting method was used to detect the protein expression levels of CDK5,MAPK and PP1 in each group mice brain tissue; qRT-PC method was used to detect the mRNA transcription levels of CDK5,MAPK and PP1 in mice brain tissue of each group.Results Compared with normal control group, the average optical density of P39 and the total number of positive neurons in the hippocampus and cerebral cortex of other groups were significantly increased, the mRNA and protein expression levels of CDK5 and MAPK1 were significantly increased, the expression levels of PP1 mRNA and protein were significantly decreased(all P<0.05);compared with the model group, the average optical density of P39 and the total number of positive neurons in the hippocampus and cerebral cortex of TSG groups were significantly decreased, the mRNA and protein expression levels of CDK5 and MAPK1 were significantly decreased, the expression levels of PP1 mRNA and protein were significantly increased(all P<0.05).Conclusions TSG could improve APP/PS1/Tau transgenic AD mouse.The effects of which may be associated with down-regulating the protein expressions and gene transcription levels of CDK5,MAPK1 and up-regulating the protein expressions and gene transcription levels of PP1,inhibiting Tau protein phosphorylation.更多还原