Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Clin Exp Pharmacol Physiol. 2021 Jun;48(6):837-845. doi: 10.1111/1440-1681.13470. Epub 2021 Feb 1.
Ethanol-induced myocardial injury involves multiple pathophysiological processes including apoptosis. Empagliflozin (EMPA), is a novel hypoglycaemic drug which possesses multiple pharmacologically relevant protective effects, including anti-apoptotic, anti-inflammatory and antioxidant effects. However, whether EMPA treatment has a protective effect on ethanol-induced myocardial injury has not been assessed, to the best of our knowledge. Therefore, the aim of this study was to determine the effect of EMPA treatment on ethanol-induced myocardial injury and the underlying mechanism. An ethanol-induced myocardial injury model was established by culturing H9c2 cells treated with 200 mmol/L ethanol for 24 hours, and additional groups of ethanol treated cells were also treated with EMPA with or without SIRT1 inhibitors prior to ethanol treatment. Cell viability and apoptosis were assessed using a CCK-8 assay and flow cytometry, respectively. The expression of apoptosis-related proteins was assessed using western blotting. The results showed that EMPA pretreatment resulted in increased cell viability and a decrease in LDH activity. Moreover, EMPA pretreatment significantly reduced apoptosis of cardiomyocytes, and reduced the expression of cleaved caspase 3. Furthermore, EMPA increased the expression of SIRT1, increased the phosphorylation levels of Akt, and reduced the expression of PTEN. EMPA also reduced ethanol-induced mitochondrial apoptosis, increasing the Bcl-2/Bax ratio and the mitochondrial membrane potential. However, the cardioprotective effects of EMPA were abrogated when cells were pretreated with a SIRT1 inhibitor. In conclusion, EMPA can alleviate ethanol-induced myocardial injury by inhibiting mitochondrial apoptosis via the SIRT1/PTEN/Akt pathway. Therefore, EMPA may be a novel target for treatment of ethanol-induced myocardial injury.
乙醇诱导的心肌损伤涉及多种病理生理过程，包括细胞凋亡。恩格列净（EMPA）是一种新型降糖药物，具有多种药理相关的保护作用，包括抗凋亡、抗炎和抗氧化作用。然而，据我们所知，EMPA 治疗是否对乙醇诱导的心肌损伤具有保护作用尚未得到评估。因此，本研究旨在确定 EMPA 治疗对乙醇诱导的心肌损伤的影响及其潜在机制。通过培养用 200mmol/L 乙醇处理 24 小时的 H9c2 细胞建立乙醇诱导的心肌损伤模型，并在乙醇处理前用 SIRT1 抑制剂对乙醇处理的细胞进行 EMPA 处理。用 CCK-8 法和流式细胞术分别评估细胞活力和细胞凋亡。用 Western blot 法评估凋亡相关蛋白的表达。结果显示，EMPA 预处理可提高细胞活力并降低 LDH 活性。此外，EMPA 预处理可显著减少心肌细胞凋亡，降低 cleaved caspase 3 的表达。此外，EMPA 可增加 SIRT1 的表达，增加 Akt 的磷酸化水平，并降低 PTEN 的表达。EMPA 还减少了乙醇诱导的线粒体凋亡，增加了 Bcl-2/Bax 比值和线粒体膜电位。然而，当细胞用 SIRT1 抑制剂预处理时，EMPA 的心脏保护作用被阻断。综上所述，EMPA 可通过 SIRT1/PTEN/Akt 通路抑制线粒体凋亡从而减轻乙醇诱导的心肌损伤。因此，EMPA 可能是治疗乙醇诱导的心肌损伤的一种新靶点。
