首页|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

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

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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.
Effects of Xixin Decoction on PI3K/AKT/GSK-3β pathway in insulin-resistant Alzheimer's disease mice
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.

Xixin DecoctionAlzheimer's disease(AD)Insulin resistance(IR)PI3K/AKT/GSK-3 β pathway

周源、王郁金、屈杰、王楠、陈连吉、武姗姗、张琪、第五永长

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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

洗心汤 阿尔茨海默病 胰岛素抵抗 PI3K/AKT/GSK-3 β通路

国家自然科学基金国家自然科学基金陕西中医药大学学科创新团队项目陕西省重点研发计划陕西省重点研发计划陕西省教育厅重点科研计划咸阳市科学技术研究发展计划陕西中医药大学校级项目陕西中医药大学校级项目

82074380820745032019-QN052020SF-3362023-YBSF-61522JS010L2022ZDYFSF0552020GP412021GP01

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(3)
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