Delta opioid receptor agonist attenuates Lipopolysaccharide-induced myocardial dysfunction through enhancing mitophagy

Abstract

Objectives:To explore the molecular mechanisms of the protective effects of δ-opioid receptor agonist DADLE（[D-Ala2，D-Leu5]-enkephalin）on myocardial dysfunction in sepsis Methodology: First, we observed the effects of DADLE immediately or 4h later treatment on the survival rate of endotoxemic mice. Then, we studied the dynamic changes of autophagy and mitophagy in myocardial during sepsis. Futuremore, septic mice were treated with DADLE, opioid receptor agonist antagonist Naltrindole and their co-treatment, the level of cTnI and mitochondrial membrane potential (MMP) were evaluated. At the same time, the level of mitophagy were detected by Western blot and Transmission electron microscopic. Results:.Both immediately or post-treatment with DADLE could improve the survival rate of endotoxemic mice. The level of autophagy and mitophagy reached a peak at 6h and 12h respectively,and then gradually decreased. In addition, DADLE could reduce the level of cTnI and revert the level of MMP decreasement. The level of autophagy and mitophagy were significantly increased with DADLE treatment. Conclusion: The autophagy stress induced by LPS treatment is probably happens earlier in myocardial mitochondria. DADLE could improve the survival and protect myocardial dysfunction in endotoxemic mice.It was related to the increase of autophagy and mitophagy.