Abstract: AIM: To observe the protective effects and mechanism of Helix B surface peptide(HBSP) in rat myocardial ischemia/reperfusion injury.METHODS: Eighty-two Sprague Dawley rats(200-250 g) were randomly divided into five groups: sham group(n=18),ischemia/reperfusion(I/R) group(n=18),erythropoietin(EPO) group(3000 U/kg,4 ml/kg,n=18),HBSP group(60 μg/kg,4 ml/kg,n=18) and HBSP+LY294002 group(n=10).EPO or HBSP was injected from tail veins 5 min before reperfusion.Hemodynamic values were measured via a cannula inserted into the right common carotid artery,and cardiac functions were evaluated by echocardiograph 24 h and 1 week after reperfusion.Infarct size was measured by TTC staining and the area at risk was assessed by Evans blue staining.Expressions of Akt and phospho-Akt were detected by Western blotting and apoptosis of cardiomyocytes was detected by TUNEL.RESULTS: Compared with those in I/R group,hemodynamic values of LVSP and ±dp/dtmax and cardiac functions improved after 24 h and 1 week in EPO group and HBSP group.The infarct size also reduced and cardiomyocyte apoptosis was inhibited.Cardiomyocyte apoptosis was partially inhibited after blocking the levels of PI3K-Akt in HBSP+LY294002 group(P<0.05).The expressions of phospho-Akt were upregulated by HBSP and the apoptotic index of cardiomyocytes in HBSP+LY294002 group was higher than that in HBSP group(P<0.05).Hemodynamic values and cardiac functions after 24 h and 1 week in the other groups were lower compared with those in sham-operated group,and the infarct size and apoptotic index of cardiomyocytes were higher than those in sham group(P<0.05).No statistically significant differences were found between EPO group and HBSP group.CONCLUSION: Helix B surface peptide could markedly improve heart functions and decrease the infarct size and myocardial apoptosis induced by ischemia/reperfusion injury in in vivo rats.Its protective effects may possibly be through the activation of PI3K-Akt signal pathway.