Objective:To investigate the effects of tanshinone ⅡA(Tan ⅡA)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury and nuclear factor E2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway in hippocampal neurons.Method:HT22 cells of mouse hippocampal neurons were cultured in vitro and which in logarithmic growth period was used as experimental cell.And the Control group,model(OGD/R)group,Tan ⅡA(5μg/ml)group,Nrf2 agonist tert-butylhydroquinone(TBHQ,1.6μg/ml)group and Tan ⅡA(5μg/ml)+TBHQ(1.6μg/ml)group were set up.After 2h of treatment in each group,except for the Control group,the OGD/R damaged HT22 cell model was prepared by reoxygenation for 24h after 6h of oxygen-glucose deprivation.Cell viability was detected by MTT method,cell apoptosis rate was detected by flow cytometry,reactive oxygen species(ROS)content was detected by dichlorofluorescein diacetate(DCFH-DA)probe method,malondialdehyde(MDA)content was detected by thiobarbituric acid method,and superoxide dismutase(SOD)and catalase(CAT)activities were detected by xanthine oxidation method and ammonium molybdate method.Real-time fluorescent quantitative polymerase chain reaction(RT-PCR)and Western Blotting were used to detect mRNA and protein ex-pression related to Nrf2/HO-1 signaling pathway.Results:Compared with the OGD/R group,the activity of HT22 cells in Tan ⅡA group,TBHQ group and Tan ⅡA+TBHQ group were significantly increased,and the apoptosis rate was significantly decreased(P<0.05).The content of ROS,MDA were significantly decreased,and the activ-ity of SOD,CAT were significantly increased(P<0.05).The mRNA and protein expression of Nrf2,HO-1 were significantly increased,the protein expression of B lymphoblastoma 2(Bcl-2)was significantly increased,the pro-tein expression of Bcl-2 associated X protein(Bax),Cleaved Caspase-3 and the ratio of Bax/Bcl-2,Cleaved Caspase-3/Caspase-3 were significantly decreased(P<0.05).Tan ⅡA+TBHQ group had significantly better regulation on the detection indicators than those of Tan ⅡA group and BHQ group(P<0.05).Conclusion:Tan ⅡA can inhibit oxidative stress injury and apoptosis of OGD/R damaged hippocampal neurons,which mechanism may be related to up-regulation of Nrf2/HO-1 signaling pathway.