基于PI3K/AKT/FoxO3a信号通路探讨奇任醇对脑缺血/再灌注大鼠氧化应激损伤的影响OA

Aim To investigate the effect of kirenol on oxidative stress injury in rats with cerebral isch-emia/reperfusion injury based on PI3K/AKT/FoxO3a signaling pathway.Methods Thread embolism was used to establish rat model of cerebral ischemia/reper-fusion injury by middle cerebral artery occlusion.Then the rats were divided into the sham group,model group(MCAO group),kirenol low-dose,medium-dose and high-dose groups(1.25,2.5,5 mg·kg-1),and nimodipine group(NMDP).The kirenol groups were given drug intervention once a day for seven days.The mNSS Scores and Corner test were used to evaluate the effect of kirenol on neural function in rats.Nissl staining and TUNEL staining were used to observe the ischemic cerebral cortex tissue in rats.The kit was employed to detect kirenol effects on the levels of SOD,GSH,MDA and CAT.DCFH-DA probe was used to detect the ROS level in ischemic ce-rebral cortex of rats.The protein expressions of cleaved caspase-3,caspase-3,Bax,Bcl-2,NeuN,SOD2,PI3K,AKT,p-AKT and p-FoxO3a were de-tected by Western blot.Results Compared with MCAO group,kirenol intervention significantly re-duced mNSS score and corner turning percentage(P<0.01),improved the degree of neuron damage in rats,and reduced the number of TUNEL-positive cells(P<0.01).Compared with MCAO group,the levels of SOD,GSH and CAT in MCAO group significantly in-creased,while the levels of MDA and ROS signifi-cantly decreased after kirenol intervention(P<0.01).Furthermore,compared with MCAO group,the pro-tein expressions of Bcl-2,NeuN,SOD2,PI3K,p-AKT/AKT and p-FoxO3a in MCAO group significantly increased,and the protein expressions of Bax and cleaved caspase-3/caspase-3 protein expression ratio significantly decreased after kirenol intervention(P<0.01).Conclusions Kirenol may inhibit apoptosis and reduce oxidative stress injury in MCAO rats by regulating PI3K/AKT/FoxO3a signaling pathway,thus playing a neuroprotective role.