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.

中文翻译：

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舒芬太尼通过上调Sestrin 2表达和激活AMPK信号通路减轻心肌缺血再灌注损伤的炎症和氧化应激

摘要 本研究探讨舒芬太尼（一种亲脂性阿片类药物）是否可以通过调节 Sestrin 2 (Sesn2) 表达来防止心肌缺血再灌注 (I/R) 损伤。测定舒芬太尼给药后心肌I/R患者血液中Sesn2的表达。应用 H9c2 细胞通过氧-葡萄糖剥夺和再氧合 (OGD/R) 建立 I/R 损伤。用5、10和20μmol/L舒芬太尼处理后，检测Sesn2的表达。然后，将shRNA-Sesn2转染到H9c2细胞中。通过试剂盒依次测定肌酸激酶（CK）、CK同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）、炎症相关因子和氧化相关因子的浓度。利用蛋白质印迹来确定 AMP 活化蛋白激酶 (AMPK) 途径蛋白的表达。结果显示，患者服用舒芬太尼后，Sesn2的表达增加。OGD/R 干预上调了 Sesn2 的表达，在用舒芬太尼治疗后，Sesn2 的表达继续以剂量依赖性方式增加。此外，舒芬太尼减弱了 H9c2 细胞中由 OGD/R 诱导的 CK、CK-MB 和 cTnl 的浓度。这种效果在 Sesn2 沉默后被逆转。同时，舒芬太尼处理细胞时炎症因子和氧化应激水平显着降低，转染shRNA-Sesn2后这些抑制作用减轻。此外，舒芬太尼增强了 AMPK 及其下游乙酰辅酶 A 羧化酶 (ACC) 的磷酸化，而 Sesn2 沉默抑制了上述蛋白质的表达。