Based on AMPK/mTOR/ULK1 pathway to explore the molecular mechanism of autophagy and the intervention effect of esmolol in septic myocardial injury

Abstract Purpose Autophagy is a double-edged sword. The purpose of this study was to investigate the signal transduction pathway of esmolol (ES) interfered with lipopolysaccharide (LPS)-induced cardiomyocyte autophagy. Methods Sepsis was induced by intraperitoneal injection of LPS (10mg/kg) in male Sprague- Dawley rats (250–300) g, which were treated with ES (15mg/kg·h), 3-methyladenine (3-MA, 15mg/kg) and rapamycin (RAP, 4mg/kg) respectively for twelve hours. The severity of myocardial necrosis was analyzed by hematoxylin- eosin (HE) staining. The expression quantity of autophagy protein in myocardial tissue was detected by Western blotting. Results LPS-induced increase in the expression of p- mTOR as well as decrease in the expression of LC3-II, Beclin-1, p-AMPK and p-ULK1 was also inhibited by pretreatment with ES or rapamycin (agonists of autophagy). On the contrary, 3-MA didn’t play a role in enhancing LPS-induced autophagy inhibition. Conclusion This study suggests that ES may provide a new strategy for treatment of sepsis cardiomyopathy through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.