洗心汤对胰岛素抵抗的阿尔茨海默病小鼠PI3K/AKT/GSK-3β通路的影响

Effects of Xixin Decoction on PI3K/AKT/GSK-3β pathway in insulin-resistant Alzheimer'sdiseasemice

目的:探究洗心汤对胰岛素抵抗(IR)的阿尔茨海默病(AD)小鼠模型中PI3K/AKT/GSK-3β通路的影响,阐明其缓解AD中IR及AD症状的分子机制。方法:通过高脂喂养APP/PS1小鼠并腹腔注射低浓度链脲佐菌素(STZ)构建AD-IR小鼠模型,然后给予洗心汤灌胃治疗。Morris水迷宫检测小鼠的学习记忆能力,血糖仪检测小鼠空腹血糖水平,ELISA检测小鼠空腹胰岛素水平,试剂盒检测ROS、MDA、GSH-Px、SOD,蛋白质印迹检测小鼠脑组织中相关蛋白的表达水平。结果:AD-IR组小鼠较对照组逃避潜伏期显著增加(P<0.05),目标平台象限滞留时间与穿越平台次数均显著减少(P<0.05),空腹血糖、血清空腹胰岛素、胰岛素抵抗值升高(P<0.05),脑组织中ROS和MDA升高(P<0.05),SOD和GSH-Px降低(P<0.05),GLUT4、p-PI3K、p-AKT、p-GSK-3β、Bcl-2蛋白降低(P<0.01),IRS1pS307、IRS1pS612、IRS1pS636、Aβ42、p-Tau、Bax、cleaved caspase-3蛋白升高(P<0.01)。经洗心汤治疗后,上述指标均显著改善(P<0.05,P<0.01)。结论:洗心汤能够激活AD-IR小鼠PI3K/AKT/GSK-3β通路,缓解小鼠脑组织中的IR,减轻AD症状及其诱导的损伤。

Objective:To explore the effects of Xixin Decoction on the PI3K/AKT/GSK-3βpathway in mouse model of Alzheimer's disease(AD)with insulin resistance(IR),and to clarify its molecular mechanism for relieving IR and AD symptoms in AD.Methods:The AD-IR mouse model was constructed by feeding APP/PS1 mice with high fat and intraperitoneal injection of low-concentration streptozotocin(STZ),and then was treatment with Xixin Decoction gavage.The learning and memory ability of mice was detected by Morris water maze test;fasting blood glucose level of mice was detected by blood glucose meter;fasting insulin level of mice was detected by ELISA;ROS,MDA,GSH-Px,SOD were detected by kits;Western Blot was detected protein levels in mouse brain tissue.Results:Compared with the control group,the escape latency of the AD-IR group was significantly increased(P<0.05),the retention time of the target platform quadrant and the number of crossing the platform were significantly decreased(P<0.05).The fasting blood glucose,the serum fasting insulin and insulin resistance were increased(P<0.05).ROS and MDA were increased(P<0.05),SOD and GSH-Px were decreased(P<0.05).