Tetramethylprazine attenuates myocardial ischemia/reperfusion injury through modulation of autophagy.

The current study aimed to investigate the effects of tetramethylprazine (TMP) on myocardial ischemia/reperfusion (MI/R) injury and its underlying mechanisms. MI/R rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. CK level and LDH activity were detected to evaluate MI/R and H/R injury. Cell viability was determined by cell counting kit-8 (CCK-8) assay. Cell apoptosis were identified by flow cytometry and autophagy were detected by western blot. Treatment with TMP significantly reduced CK level and LDH activity and decreased myocardial infarct size in MI/R rats. TMP reduced autophagy dysfunction induced by MI/R. Moreover, TMP treatment decreased H/R-induced injury and attenuated autophagy dysfunction in cardiomyocytes. Inhibiting autophagic flux with chloroquine (CQ) decreased the cardioprotection exerted by TMP in vivo and in vitro. Additionally, the effects of TMP on the modulation of autophagy were inhibited by LY294002 (a PI3K inhibitor) in H/R cardiomyocytes. Our findings suggested TMP exerted cardioprotection against MI/R injury by decreasing Beclin-1 associated autophagy dysfunction through PI3K pathway.