Melatonin protects against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice.

Affiliation

Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China; Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha 410011, China. Electronic address: [Email]

Abstract

OBJECTIVE : The apoptosis and autophagy play an important role in the pathogenesis of sepsis-induced cardiac dysfunction. Previous studies have demonstrated that melatonin protects against cardiac dysfunction during sepsis. In addition, silent information regulator 1 (SIRT1) is a therapeutic target for sepsis-induced myocardial dysfunction. The aims of this study were to investigate whether SIRT1 was involved in melatonin's cardioprotection during sepsis and the mechanisms.
METHODS : In this study, twenty-four male C57BL/6 mice were randomly assigned to four groups: Control group, LPS group, LPS + Melatonin group and LPS + Melatonin + EX527 group. Mice were treated with lipopolysaccharide for 8 h with or without melatonin or EX527. The cardiac function, myocardial injury biomarkers, cardiac histopathology, cardiomyocyte apoptosis, autophagosome as well as the protein expressions of SIRT1, cleaved caspase-3, LC3-II/LC3-I ratio and p62 in the myocardium were assayed.
RESULTS : The results demonstrated that melatonin significantly improved cardiac function, decreased creatine kinase (CK) and creatine kinase-MB (CK-MB) levels, attenuated myocardial architecture destruction, inhibited cardiomyocyte apoptosis and increased cardiac autophagy as compared with the LPS group. In addition, melatonin significantly increased SIRT1 protein expression in the myocardium of mice with sepsis, while inhibition of SIRT1 by EX527 abolished melatonin's cardioprotection during sepsis.
CONCLUSIONS : In this study, we found that melatonin protected against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice.

Keywords

Apoptosis,Autophagy,Cardiac dysfunction,Melatonin,SIRT1,Sepsis,