ICS Ⅱ Ameliorated Cerebral Ischemia-reperfusion Injury And Investigate Its Mechanism

Objective: To explore the effects of icariside Ⅱ(ICS Ⅱ)on cerebral ischemia-reperfusion(I/R)injury and its underlying mechanism.Methods: The focal cerebral ischemia reperfusion model was established by middle cerebral artery occlusion(MCAO).108 male Sprague Dawley(SD)rats were randomly divided into 6 group: Sham group,Sham group + ICS Ⅱ high-dose group(16 mg/kg),I/R group,I/R + ICSⅡ low-dose(4 mg/kg)group,middle-dose(8 mg/kg)group,and high-dose group(16 mg/kg).After the I/R model in rats were established successfully,the ICS Ⅱ-treated groups rats were intr gastrically administered with ICS Ⅱ at the dose of 4,8,16 mg/kg twice a day,consecutively 3 days and 7 days,while Sham and I/R group rats were intragastrically administered with volume-matched vehicle,instead.Thereafter,the neurological score,the cerebral infarction volume,the brain water content,SOD,MDA levels and ROS contents were detected by Longa 5 method,TTC dye,drywet weight method,and ELISA assay,respectively.Furthermore,the protein expressions of LC3 B,Beclin1,keap1,cytoplasm-Nrf2,nucleus-Nrf2,NQO-1,HO-1,GCLM,GCLC were detected by Western blot.Results: The results showed that neurological score,cerebral infarct volume and water content were dramatically increased in I/R group than those of sham group,evidenced by Longa 5 method,TTC dye and drywet weight method,respectively.Besides,the results of ELISA assay showed that the SOD levels was decreased,while,ROS contents and MDA levels were obviously increased in I/R group than those of sham group.Furhtermore Western blot results indicated that the protein expressions of LC3 B,Beclin1,keap1,nucleus-Nrf2,cytoplasm-Nrf2 were increased in I/R group compared with Sham group,while,the expressions of NQO-1,HO-1,GCLM and GCLC were obviously decreased in I/R group than those of sham group.However,ICS Ⅱ significantly improved neurological function score,reduced cerebral infarction volume and the brain water content.Moreover,ICS Ⅱ also enhanced SOD levels and decreasd ROS contents and MDA levels.Furthermore.ICS Ⅱ significantly upregulated the expressions of nucleus-Nrf2,NQO-1,HO-1,GCLM,GCLC,and downregulated the expressions of LC3 B,Beclin1,keap1 andcytoplasm-Nrf2.Conclusion: ICS Ⅱ ameliorated MCAO-induced I/R injury in rats and its underlying mechanism maybe related regulating Nrf2 signaling pathwas,thereby inhibiting excessive autophagy.