Sufentanil attenuates inflammation and oxidative stress in myocardial ischemia reperfusion injury via upregulating Sestrin 2 expression and activating AMPK signalling pathway

Abstract

This study explored whether sufentanil, a lipophilic opioid, can protect against myocardial ischemia-reperfusion (I/R) injury via regulating Sestrin 2 (Sesn2) expression. The expression of Sesn2 was measured in the blood of patients with myocardial I/R after sufentanil administration. H9c2 cells were applied to establish I/R injury by oxygen-glucose deprivation and reoxygenation (OGD/R). After treatment with 5, 10 and 20 μmol/L sufentanil, the expression of Sesn2 was examined. Then, shRNA-Sesn2 was transfected into H9c2 cells. The concentrations of creatine kinase (CK), CK isoenzymes (CK-MB), cardiac troponin I (cTnI), inflammation-related factors and oxidative-related factors were sequentially determined by kits. Western blotting was exploited to determine the expression of AMP-activated protein kinase (AMPK) pathway proteins. The results revealed that the expression of Sesn2 was increased in patients after administration with sufentanil. OGD/R intervention upregulated the expression of Sesn2, which continued to increase in a dose-dependent manner following treatment with sufentanil. Moreover, sufentanil attenuated the concentrations of CK, CK-MB and cTnl induced by OGD/R in H9c2 cells. This effect was reversed after Sesn2 silencing. Meanwhile, the levels of inflammatory factors and oxidative stress were notably decreased when cells were treated with sufentanil, and these inhibitory effects were alleviated after transfection with shRNA-Sesn2. Furthermore, sufentanil enhanced the phosphorylation of AMPK and its downstream acetyl CoA carboxylase (ACC), whereas Sesn2 silencing inhibited the expression of the above proteins. These findings demonstrated that sufentanil could attenuate inflammation and oxidative stress in myocardial I/R injury via upregulating Sesn2 expression and activating the AMPK pathway.

Keywords

• ischemia reperfusion
• sufentanil
• inflammation
• oxidative stress
• sestrin 2