基于磷脂酰肌醇3激酶/蛋白激酶B信号通路探究麦冬皂苷D对脑缺血再灌注损伤的神经保护作用OA

Objective:To explore the neuroprotective effect of ophiopogonin D(OPD)alone or in combination with Edaravone on cerebral ischemia-reperfusion injury(CIRI)by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:A total of 120 female C57BL/6 mice were randomly assigned to five groups(n=24 per group):Sham group,cerebral ischemia-reperfusion(MCAO/R)group,OPD group,edaravone group,and OPD+edaravone group.Middle cerebral artery occlusion-reperfusion(MCAO/R)mod-els were established in mice,followed by daily drug administration according to group assignments after 1 hour of cerebral ischemia,lasting for 7 days.Body weight and neurological behavior scores were recorded daily.Motor func-tion was evaluated using rotarod and open field tests,cerebral blood flow recovery was monitored by laser speckle im-aging,cerebral infarct volume was measured by TTC staining,and inflammatory cell infiltration and neuronal mor-phology were assessed via HE and Nissl staining.Western blotting was used to examine protein expression in the is-chemic penumbra regions.Results:On day 5 and day 7 post-modeling,body weight was significantly higher in OPD,edaravone,and OPD+edaravone groups compared to the MCAO/R group(all P＜0.01).Zea-Longa neurological scores showed that neurological deficits were significantly alleviated on day 5 and day 7 in all three treatment groups compared to the MCAO/R group(all P＜0.05).The three treatment groups exhibited prolonged retention time and increased locomotion distance on day 3 and day 7(all P＜0.05).Regional cerebral blood flow(rCBF)ratios were significantly increased in OPD,edaravone,and OPD+edaravone groups at 3 and 7 days post-reperfusion(all P＜0.05),accompanied by markedly reduced cerebral infarct volumes(P＜0.001).HE and Nissl staining revealed atten-uated brain tissue damage,reduced inflammatory cell infiltration,improved neuronal apoptosis,and preserved Nissl bodies in all treatment groups.Western blotting demonstrated that compared to the MCAO/R group,treatment groups showed upregulated Arg1 and Bcl-xL expression,increased ratios of p-PI3K/PI3K and p-AKT/AKT,and downregulated Iba1 and iNOS expression(all P＜0.05).Notably,Iba1 and iNOS expression levels in the OPD+edaravone group were significantly lower than those in either the OPD or edaravone monotherapy groups(all P＜0.05).Conclusion:Ophiopogonin D alone or combined with edaravone effectively alleviates weight loss,neurological deficits,and motor dysfunction following cerebral ischemia-reperfusion injury,exerting anti-inflammatory and anti-apoptotic effects through activation of the PI3K/AKT signaling pathway.