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's disease mice
周源 1王郁金 2屈杰 2王楠 2陈连吉 2武姗姗 2张琪 3第五永长4
作者信息
- 1. 陕西中医药大学,咸阳 712046;陕西省中医体质与疾病防治研究重点实验室,咸阳 712046;陕西省中医脑病学重点实验室,咸阳 712046
- 2. 陕西中医药大学,咸阳 712046
- 3. 陕西省中医体质与疾病防治研究重点实验室,咸阳 712046;陕西省中医脑病学重点实验室,咸阳 712046
- 4. 陕西中医药大学,咸阳 712046;陕西省中医脑病学重点实验室,咸阳 712046
- 折叠
摘要
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-3 β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问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-3 β、Bcl-2蛋白降低(P＜0.01),IRS1 pS307、IRS1 pS612、IRS1 pS636、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-3 β通路,缓解小鼠脑组织中的IR,减轻AD症状及其诱导的损伤.
Abstract
Objective:To explore the effects of Xixin Decoction on the PI3K/AKT/GSK-3 β pathway 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).GLUT4,p-PI3K,p-AKT,p-GSK-3 β,Bcl-2 protein were decreased(P＜0.01),while IRS1 pS307,IRS1 pS612,IRS1 pS636,A β 42,p-Tau,Bax,and cleaved caspase-3 were increased(P＜0.01).After the model mice were treated with Xixin Decoction,the above indicators significantly improved(P＜0.05,P＜0.01).Conclusion:Xixin Decoction could activate the PI3K/AKT/GSK-3 β pathway in the AD-IR mouse model to alleviate insulin resistance in the mouse brain,and alleviate AD symptoms and AD-induced damage.
关键词
洗心汤/阿尔茨海默病/胰岛素抵抗/PI3K/AKT/GSK-3/β通路Key words
Xixin Decoction/Alzheimer's disease(AD)/Insulin resistance(IR)/PI3K/AKT/GSK-3 β pathway引用本文复制引用
基金项目
国家自然科学基金(82074380)
国家自然科学基金(82074503)
陕西中医药大学学科创新团队项目(2019-QN05)
陕西省重点研发计划(2020SF-336)
陕西省重点研发计划(2023-YBSF-615)
陕西省教育厅重点科研计划(22JS010)
咸阳市科学技术研究发展计划(L2022ZDYFSF055)
陕西中医药大学校级项目(2020GP41)
陕西中医药大学校级项目(2021GP01)
出版年
2024
NETL
NSTL
万方数据