Remifentanil attenuates lipopolysaccharide-induced oxidative injury by downregulating PKCß2 activation and inhibiting autophagy in H9C2 cardiomyocytes.

AIM: Lipopolysaccharide (LPS)-induced myocardial injury is a leading cause of death in patients with sepsis, which is associated with excessive activation of PKCß (especially PKCß2) and autophagy. Remifentanil, a µ-opioid receptor agonist, is well demonstrated to have beneficial effects during sepsis, but the underlying mechanisms are still unknown. The present study was designed to investigate the roles of remifentanil in PKCß2 and autophagy in LPS-treated cardiomyocytes. MAIN METHODS: H9C2 cardiomyocytes were treated with or without remifentanil (2.5 µM), PKCß2 inhibitor CGP53353 (CGP, 1 µM) or autophagy inhibitor 3-methyladenine (3-MA, 10 µM) in the presence or absence of LPS (10 µg/mL). KEY FINDINGS: LPS exposure for 24 h led to a significant increase in cell death, LDH release and MDA production in H9C2 cardiomyocytes, accompanied with decreased SOD activity and excessive PKCß2 activation and autophagy indicated by enhanced Beclin-1 and LC-3II expression and decreased p62 expression. All these changes were attenuated by remifentanil intervention. In addition, inhibition of LPS-induced PKCß2 activation by CGP or autophagy inhibitor 3-MA has similar effects to remifentanil. SIGNIFICANCE: Remifentanil protects H9C2 cardiomyocytes against LPS-induced oxidative injury, as a result of downregulating PKCß2 activation and inhibiting autophagy, partially.