白藜芦醇通过PI3K/Akt信号通路改善血管性痴呆大鼠认知功能作用机制OA

Objective:To investigated effects of resveratrol on cognitive function and hippocampal neuronal ap-optosis in a vascular dementia(VD)rat model,and explored whether it exerts neuroprotective effects through the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods:Sixty-eight male sprague-dawley rats were randomly divided into seven groups:sham group,model group,low-dose,medium-dose,and high-dose resveratrol groups,donepezil group,and combined treatment group,with 8-10 rats per group.Modified transient bilateral common carotid artery occlusion method was used to establish the VD rat model,followed by four weeks of continuous intervention.The low-dose,medium-dose,and high-dose resveratrol groups received oral gavage of 12.5,25,and 50 mg/kg,respectively.The donepezil group received 0.45 mg/kg donepezil via oral gavage,and the combined treatment group received 25 mg/kg resveratrol orally plus 5 mg/kg LY294002 intraperitoneally.Cognitive function was assessed using the Y-maze test.Neuronal morphology in the hippocampal CA1 region was examined by hematox-ylin-eosin(HE)and Nissl staining.Neuronal apoptosis was detected by TUNEL staining.Aprotein expression levels of B-cell lymphoma-2(Bcl-2),Caspase-3,Caspase-9,and PI3K/Akt pathway-related proteins were analyzed by West-ern blot.Results:Compared with the sham group,the model group exhibited impaired cognitive function(P＜0.05),severe neuronal morphological damage in the hippocampal CA1 region,and increased apoptosis index(P＜0.05).Ex-pression of Caspase-9 and Caspase-3 was elevated,while Bcl-2 expression was reduced(P＜0.05).Phosphorylation levels of PI3K and Akt were decreased(P＜0.05).Compared with the model group,all resveratrol-treated groups showed improved cognitive function(P＜0.05),repaired neuronal pathological damage,reduced apoptosis index(P＜0.05),downregulated expression of Caspase-9 and Caspase-3(P＜0.05),and upregulated expression of Bcl-2 as well as phosphorylated PI3K and Akt(P＜0.05).However,after combined treatment with LY294002,the neuropro-tective and anti-apoptotic effects of resveratrol were reversed(P＜0.05).Conclusion:Resveratrol improves learning and memory ability in VD rat models,reduces hippocampal neuronal injury,and inhibits neuronal apoptosis,mecha-nisms closely associated with activation of the PI3K/Akt signaling pathway.