蛹虫草提取物改善老年大鼠骨骼肌缺血再灌注后认知功能的机制研究OACHSSCD

Objective:To investigate the effects and mechanisms of Cordyceps militaris extract in improving cognitive function after skeletal muscle ischemia-reperfusion in elderly rats by regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods:Rats were randomly divided into a sham operation group,model group,low-dose C.militaris extract group,high-dose C.militaris extract group,and high-dose C.militaris extract+ML385 group using a ran-dom number table.A limb ischemia-reperfusion injury(LIR)model was established.Rats were treated with C.militaris extract and the Nrf2 inhibitor ML385 according to grouping.Cognitive function,pathological morphology of gastrocnemius muscle,apoptosis of hippocampal neurons,serum inflammatory mediator levels,oxidative stress markers in gastrocnemius muscle and brain tissues,and the expression of Nrf2/ARE pathway-related proteins in gastrocnemius muscle and brain tissues were assessed.Results:Compared with the sham operation group,the model group showed severe damage to gastrocnemius muscle tissue.The number of errors in the dark-avoidance and step-down tests,the proportion of hippocampal neuronal apoptosis,serum levels of interleukin-1 β(IL-1 β),tumor necrosis factor-α(TNF-α),and IL-6,as well as malondialdehyde(MDA)levels in gastrocnemius muscle and brain tissues were significantly increased(P＜0.05),whereas the latency in the dark-avoidance and step-down tests,total antioxidant capacity(TAC)in gastrocnemius muscle and brain tissues,and the expression of Nrf2 and heme oxygenase-1(HO-1)proteins were signifi-cantly decreased(P＜0.05).Both low-and high-dose C.militaris extract improved the above pathological changes,with the low-dose group showing a stronger effect.The high-dose C.militaris extract+ML385 group abolished the protective effects of C.militaris extract on these pathological indicators in LIR model rats.Conclusion:C.militaris extract alleviates skeletal muscle ischemia-reper-fusion injury and improves cognitive function in aged rats by activating the Nrf2/ARE signaling pathway,thereby inhibiting neuroin-flammation and oxidative stress.