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OA北大核心CSTPCDMEDLINE

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.