黄芪甲苷通过Nrf2/HO-1 通路减轻缺血性脑卒中大鼠氧化应激损伤及改善眩晕症状的机制OA

Objective:To explore the mechanism of astragaloside Ⅳ in reducing oxidative stress injury and improving vertigo symptoms in rats with ischemic stroke through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods:Sham operation group(sham group),model group(MCAO group),positive control group(XST group),ASIV group,Nrf2 activator group(Hesperin group),Nrf2 inhibitor group(Brusatol group)(10 rats in each group).Middle cerebral artery occlusion(MCAO)model was established in all groups except sham group.Sham group and MCAO group were not given any intervention.The XST group was given Xuesaitong capsule by gavage(3.15 mg/kg),the ASIV group was given astragaloside Ⅳ by gavage(20 mg/kg),the Hesperin group was given astragaloside Ⅳ by gavage(20 mg/kg)+injection of Hesperin(10 mg/kg),and the Brusatol group was given astragaloside Ⅳ by gavage(20 mg/kg)+injection of Brusatol(2 mg/kg).All groups were continuously intervened for 7 days.After intervention,Zea Longa score and Garcia JH score were used to evaluate neurological function.Centrifuge and jumping instrument were used to observe vertigo symptoms,the body weight of rats in each group was recorded and compared;the contents of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and oxidized glutathione,glutathione disulfide(GSSG)in hippocampus were detected by chemical colorimetry.HE staining was used to observe the morphology of frontal lobe brain tissue.The expression of HO-1 and Nrf2 protein was detected by Western blot.Results:Compared with sham group,Zea Longa score,latency,MDA and GSSG levels in MCAO group,XST group,ASIV group,Hesperin group and Brusatol group were increased,Garcia JH score,body weight,rotation time,SOD,GSH levels,Nrf2 and HO-1 protein expression were decreased(P<0.05).Compared with MCAO group,Zea Longa score,latency,MDA and GSSG levels in XST group,ASIV group and Hesperin group decreased,and those in Hesperin group were the lowest(P<0.05).Garcia JH score,body weight,rotation time,SOD,GSH levels,Nrf2 and HO-1 protein expression increased,and those in Hesperin group were the highest(P<0.05).There was no significant difference between MCAO group and Brusatol group(P>0.05).The cells in the MCAO group and the Brusatol group were disordered,and there was a large amount of inflammatory infiltration between the cells.The arrangement of cells in XST group,ASIV group and Hesperin group tended to be regular,and the morphology of Hesperin group was the best.Conclusion:Astragaloside Ⅳ is beneficial to improve neurological function and vertigo symptoms in rats with ischemic stroke,improve oxidative stress.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.