益智聪明汤对Aβ25-35致阿尔茨海默病小鼠tau蛋白磷酸化的影响

摘要

目的 观察益智聪明汤(人参、茯苓、制首乌,等)对β-淀粉样蛋白Aβ25-35致阿尔茨海默病模型小鼠磷酸化tau蛋白表达的影响及其作用机制.方法 选用SPF级ICR小鼠60只,随机分为6组,每组10只,假手术组左侧海马单次注射生理盐水3μL,模型组、盐酸多奈哌齐组及益智聪明汤各组分别左侧海马注射Aβ25-35 3μL(3 nmol/L),除假手术组及模型组外,其余各组分别灌胃给予盐酸多奈哌齐和益智聪明汤.给药15 d后,免疫组化测定tau蛋白磷酸化位点的表达;Western blot检测海马区PI3 K/AKT/GSK3β(磷脂酰肌醇-3-羟激酶/蛋白激酶B/糖原合成酶激酶3β)的蛋白表达.结果 益智聪明汤可减少tau(Thr231)及tau (Ser404)磷酸化表达水平,增加PI3K、AKT及GSK3β磷酸化表达.结论 益智聪明汤可抑制Aβ25-35致阿尔茨海默病小鼠tau蛋白磷酸化位点的表达,其机制可能是通过PI3 K/Akt/GSK3β信号途径.%AIM To study the effects of Yizhi Congming Decoction (Ginseng Radix et Rhizoma,Poria,Polygoni multiflori Radix praeparata,etc.) on learning and memory deficits through reducing tau hyperphosphorylation in Aβ-induced AD mice and its mechanism of action.METHODS Sixty ICR mice were randomly and equally assigned into six groups.Sham group (injection of 3 μL normal saline into left hippocampus),model group,donepezil group and each group of Yizhi Congming Decoction (injection of 3 μL Aβ25-35 into left hippocampus).Donepezil group and three treatment groups were gavaged with donepezil and Yizhi Congming Decoction.After 15 days of administration,immunohistochemistry was used to observe the expressions of Ser404 and Thr231.Western blot was performed to evaluate the levels of phosphatidylinositol-3-kinase (PI3K),threonine/serine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK3β).RESULTS Yizhi Congming Decoction attenuated the levels of phosphorylated tau at the Thr231 and Ser404 sites in the hippocampus and increased the phosphorylation levels of PI3K,AKT and GSK3β.CONCLUSION Yizhi Congming Decoction effectively provides protection against learning and memory deficits and inhibits hyperphosphorylated tau protein expression in the hippocampus.The possible mechanism may occur via the PI3 K/Akt-dependent GSK3 β signalling pathway.