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In this study the cardioprotective effect and molecular mechinsms of tanshinone ⅡA were investigated.Results showed that tanshinone ⅡA could protect H9c2 cells from H2O2-induced cell death concentration-dependently.MiR-133 was involved in tanshinone A action.Decreases of miR-133 expression induced by increasing concentration of H2O2 could be completely reversed by.tanshinone ⅡA treatment.Inhibition of miR-133 function by transfection of specific inhibitor abolished the cardioprotective effects of tanshinone ⅡA against H2O2-induced cell death.Furthermore, our results also showed that tanshinone ⅡA could activate Akt kinase by phossphorylation at serine 473.Inhibition the activation of PI3K/Akt signaling by pretreatment with PI3K specific inhibitor,wortmannin and LY294002, would eliminate the cardioprotective effects of tanshinone ⅡA against H202-induced cell death.We furtherly determined the Bcl-2 protein levels by western blot and found that tanshinone ⅡA could completely reverse the decreases of Bcl-2 protein induced by H2O2;but the effect of tanshinone ⅡA on Bcl-2protein in oxidative environment was suppressed by PI3K inhibitor, wortmannin, which indicated that tanshinone ⅡA exerted cardioprotective effects against H2O2-induced cell death through the activation of PI3K/Akt signal transduction pathway and consequent upregulation of Bcl-2 expression.Taken together, the present study indicates that tanshinone ⅡA is a promising natural cardio-protective agent.