基于PI3K/Akt信号通路探讨上下两济丹改善AD小鼠认知功能作用机制OA

Objective:To investigate the mechanisms by which Shangxia Liangji pills improve cognitive function in Alzheimer's disease(AD)mice based on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway,aiming to provide experimental evidence for its clinical use in AD treatment.Methods:Fifty APP/PS1 double-transgenic mice were randomly divided into a model group,Shangxia Liangji pills low-dose group,medium-dose group,high-dose group,and donepezil hydrochloride group,with 10 mice in each group.Additionally,10 C57BL/6 mice of the same genetic background were assigned to the normal group.Cognitive function was assessed using the Morris water maze and novel object recognition tests.Hippocampal pathological changes were observed using transmission electron microscopy and Nissl staining.Neuroinflammation in hippocampal tissue was detected by enzyme-linked immunosorbent assay(ELISA).Protein expression levels of PI3K/Akt pathway-related proteins,postsynaptic density protein 95(PSD95),and amyloid precursor protein(APP)in hippocampal tissue were measured by Western blot.Results:Compared with the normal group,the model group exhibited significantly increased total swimming distance and escape latency,significantly reduced number of platform crossings(P<0.01),and a decreased recognition index(P<0.01).Marked neuronal apoptosis was observed in the hippocampal region,with a marked reduction in the number of neurons in the CA3 region(P<0.01).Levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in hippocampal tissue were significantly elevated(P<0.01).APP expression in hippocampal tissue was markedly upregulated(P<0.01),while PSD95,p-PI3K/PI3K,and p-Akt/Akt protein expression were significantly downregulated(P<0.01).Compared with the model group,the Shangxia Liangji pills high-dose group showed significantly reduced total swimming distance and escape latency,significantly increased number of platform crossings(P<0.01),and an elevated recognition index(P<0.01).Hippocampal neuronal apoptosis was alleviated,with a significant increase in the number of neurons in the CA3 region(P<0.01).Levels of IL-6,IL-1β,and TNF-α were significantly decreased(P<0.01).APP expression was downregulated(P<0.05),while PSD95,p-PI3K/PI3K,and p-Akt/Akt protein expression were significantly upregulated(P<0.01).Conclusion:Shangxia Liangji pills may improve cognitive function in AD mice by modulating the PI3K/Akt pathway,thereby reducing neuroinflammation and alleviating neuronal and synaptic injury.