动物造模,阿尔茨海默症 z-bio 2022-09-23 816

　　Objective To investigate the effect of metformin on phosphatidylinositol-3-kinase/protein kinase B pathway and cognitive dysfunction in Alzheimer's disease rats.

　　Methods Fifty SD rats were selected and randomly divided into normal group (Normal group), AD model group (AD group), Met low-dose (50 mg/kg) group, and Met medium-dose (100 mg/kg) group. group and high-dose Met (200 mg/kg) group, with 10 rats in each group; except the Normal group, rats in the other groups were injected with 10 μL streptozotocin (3 mg/kg) into the bilateral ventricles to establish AD models. After successful modeling, administration was started. Met group was given the corresponding dose of Met solution by gavage, Normal group and AD group were given the same amount of normal saline by gavage, and each group was given continuous administration for 14 days, once a day. After the last administration, the spatial cognitive function of rats was detected by Morris water maze test. Rats were sacrificed, hippocampal tissue was taken, and the contents of β-amyloid protein 42 (Aβ42) and phosphorylated tau protein (p-tau) in hippocampal tissue were detected by ELISA. Pathological changes of neurons; PI3K positive expression detected by immunohistochemistry; PI3K, phosphorylated Akt (p-Akt), insulin receptor substrate-1 (insulin receptor substrate-1, IRS- 1), the relative expression level of glycogen synthase kinase-3 (GSK-3) protein.

　　Results Compared with the Normal group, the hippocampus of the AD group showed pathological damage such as disordered and reduced neuronal cells. The number of rats crossing the platform, the ratio of the swimming distance to the total distance in the original platform quadrant, and the ratio of swimming time to the total time were all obvious. The expression levels of PI3K, p-Akt and IRS-1 in the hippocampus were significantly decreased (P＜0.05), the average escape latency was prolonged (P＜0.05), the contents of Aβ42 and p-tau in the hippocampus, The expression of GSK-3 protein was significantly increased (P<0.05); compared with AD group, the pathological damage of the hippocampus of the rats in the Met low, medium and high dose groups was alleviated, and the number of times the rats crossed the platform, the swimming distance of the original platform quadrant and the total The ratio of distance and the ratio of swimming time to total time were significantly increased (P<0.05), the protein expression levels of PI3K, p-Akt and IRS-1 in hippocampus were significantly increased (P<0.05), and the average escape latency was shortened (P<0.05). 0.05), the contents of Aβ42 and p-tau in hippocampus, and the expression of GSK-3 protein were significantly decreased (P<0.05), and the above indexes in each dose group of Met were dose-dependent.

　　Conclusion Met can activate the PI3K/Akt pathway in the hippocampus of AD rats, reduce the contents of p-tau and Aβ42 in the hippocampus, and improve the cognitive impairment of AD rats.