南方医科大学学报2024，Vol.44Issue(5)：894-903,10.DOI:10.12122/j.issn.1673-4254.2024.05.11
交泰丸通过激活PI3K/AKT信号通路改善阿尔茨海默病模型小鼠大脑的葡萄糖代谢
Jiaotaiwan improves brain glucose metabolism in a mouse model of Alzheimer's disease by activating the PI3K/AKT signaling pathway
摘要
Abstract
Objective To investigate the effect of Jiaotaiwan on brain insulin-PI3K/AKT pathway in a mouse model of Alzheimer's disease(AD).Methods Fifty 3-month-old male APP/PS1 double transgenic mice were randomized into AD model group,low-,medium-and high-dose Jiaotaiwan treatment groups,and donepezil treatment group.Cognitive functions of the mice were assessed using water maze and open field tests,and neuronal pathologies were observed with HE staining and Nissl staining;immunohistochemistry was used to detect amyloid Aβ deposition in the brain.Fasting serum insulin levels of the mice were measured,and the expressions of Aβ42,insulin-PI3K/AKT pathway components and downstream glucose transporters in the brain tissue were detected with RT-qPCR and Western blotting.Results The AD mouse models exhibited obvious impairment of learning and memory abilities,significantly reduced hippocampal neurons,and obvious Aβ amyloid plaques in the brain tissue with increased Aβ42 protein expression(P<0.05)and insulin resistance index,decreased hippocampal PI3K expressions,lowered expressions of AKT and InR,reduced expressions of GLUT1,GLUT3,and GLUT4,and increased expression of GSK3β in both the hippocampus and cortex.Treatment with Jiaotaiwan and donepezil both effectively improved memory ability of the mouse models,increased the number of hippocampal neurons,reduced Aβ amyloid plaques and increased the expressions of PI3K,AKT,InR,GLUT1,GLUT3 and GLUT4 in the hippocampus and cortex.Conclusion Jiaotaiwan improves learning and memory abilities of APP/PS1 double transgenic mice and delay the development of AD by activating the PI3K/AKT pathway and regulating the expression levels of its downstream GLUTs in the brain.关键词
阿尔茨海默病/交泰丸/葡萄糖代谢/胰岛素PI3K/AKT通路/葡萄糖转运蛋白Key words
Alzheimer's disease/Jiaotaiwan/glucose metabolism/insulin PI3K/AKT pathway/glucose transporter proteins引用本文复制引用
王妍,阮毓卿,崔璨,王秀..交泰丸通过激活PI3K/AKT信号通路改善阿尔茨海默病模型小鼠大脑的葡萄糖代谢[J].南方医科大学学报,2024,44(5):894-903,10.基金项目
安徽省中医药传承创新项目(2020ccyb19) （2020ccyb19）
安徽省中医药科技攻关专项项目(202303a07020001) （202303a07020001）
安徽省重点研究与开发计划项目(2022e07020036) （2022e07020036）
