Abstract: AIM To investigate the protective effects and mechanisms of Helix B surface peptide (HBSP) against myocardial injury induced by ischemia/reperfusion in mice. METHODSMale mice (20±2 g) were randomly divided into four groups: sham group, ischemia/reperfusion group (I/R), I/R+HBSP group and I/R+HBSP+Wortmannin group (I/R+HBSP+Wort). Primary myocardial cells were randomly divided into four groups: control group, hypoxia/reoxygenation group (H/R), hypoxia/reoxygenation+HBSP group (H/R+HBSP) and hypoxia/reoxygenation+HBSP+Wortmannin group (H/R+HBSP+Wort). Cardiac functions and myocardial infarct size were evaluated. Autophagy and mitochondrion of cardiomyocytes were observed by transmission electron microscope. Expression of protein was detected by Western blotting and LC3 dots were calculated by confocal laser scanning microscope. RESULTSCompared with those in I/R group, the values of LVEF and FS in I/R+HBSP group were higher (P<0.05) and the values of myocardial infarct size and numbers of autophagy in I/R+HBSP group were reduced (P<0.05). Compared with those in I/R+HBSP group, LVEF and FS values in I/R+HBSP+Wort group were lower (P<0.05) and the values of myocardial infarct size and numbers of autophagy in I/R+HBSP+Wort group were increased (P<0.05). Compared with those in H/R group, expression of phosphor-Akt or phosphor-mTOR in H/R+HBSP group was higher (P<0.05) and LC3 dots in H/R+HBSP group were reduced (P<0.05). Compared with those in H/R+HBSP group, expression of phosphor-Akt or phosphor-mTOR in H/R+HBSP+Wort group was lower (P<0.05) and LC3 dots in H/R+HBSP+Wort group were increased (P<0.05). CONCLUSIONHelix B surface peptide attenuates myocardial ischemia/reperfusion injury by inhibiting autophagy. Its protective effect may be related to the activation of PI3K/Akt/mTOR signal pathway.