ESMOLOL PROTECTS AGAINST LPS-INDUCED CARDIAC INJURY VIA THE AMPK/mTOR/ULK1 PATHWAY IN RAT

Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.