Remifentanil attenuates lipopolysaccharide-induced oxidative injury by downregulating PKCβ2 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 PKCβ (especially PKCβ2) 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 PKCβ2 and autophagy in LPS-treated cardiomyocytes.

MAIN METHODS

H9C2 cardiomyocytes were treated with or without remifentanil (2.5 μM), PKCβ2 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 PKCβ2 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 PKCβ2 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 PKCβ2 activation and inhibiting autophagy, partially.