Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Neurological Rehabilitation, The FourthAffiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
Bioengineered. 2022 May;13(5):13162-13173. doi: 10.1080/21655979.2022.2074109.
Potential ischemia/reperfusion (I/R) injuries are commonly induced during treatment of cardiovascular diseases, such as acute myocardial infarction (AMI). It is reported that oxidative stress and over-autophagy in cardiomyocytes are involved in the pathogenesis of I/R injury. Sitagliptin is an effective inhibitor of dipeptidyl peptidase 4 (DPP-4) for the treatment of diabetes, which is recently reported to regulate oxidative stress and autophagy. The present study is designed to explore the function of Sitagliptin on I/R injury. Hypoxia/reoxygenation (H/R) condition was used to simulate the I/R injury on cardiomyocytes. We found that the declined cell viability and elevated expression level of creatine kinase myocardial band (CK-MB) were observed in the H/R group, accompanied by the increased mitochondrial reactive oxygen species (ROS), elevated cellular malondialdehyde (MDA) level, and mitochondrial dysfunction. After Sitagliptin treatment, the damages in H9c2 cardiomyocytes, oxidative stress, and mitochondrial dysfunction were significantly alleviated. In addition, the overactivated autophagy and mitophagy in H/R-challenged cardiomyocytes were dramatically mitigated by Sitagliptin, accompanied by the upregulation of SIRT3. Lastly, the protective effect of Sitagliptin on H/R-induced mitophagy, autophagy, and damages in cardiomyocytes was dramatically abolished by the knockdown of SIRT3. Taken together, our data reveal that Sitagliptin ameliorated the H/R-induced injury in cardiomyocytes by mediating sirtuin 3 (SIRT3) and autophagy.
潜在的缺血/再灌注（I/R）损伤在心血管疾病的治疗中很常见，例如急性心肌梗死（AMI）。有报道称，心肌细胞中的氧化应激和过度自噬参与了 I/R 损伤的发病机制。西他列汀是一种有效的二肽基肽酶 4（DPP-4）抑制剂，用于治疗糖尿病，最近有报道称它可以调节氧化应激和自噬。本研究旨在探讨西他列汀对 I/R 损伤的作用。缺氧/复氧（H/R）条件用于模拟心肌细胞的 I/R 损伤。我们发现，H/R 组观察到细胞活力下降和肌酸激酶同工酶心肌带（CK-MB）表达水平升高，同时伴有线粒体活性氧（ROS）增加、细胞丙二醛（MDA）水平升高和线粒体功能障碍。西他列汀治疗后，H9c2 心肌细胞的损伤、氧化应激和线粒体功能障碍明显减轻。此外，西他列汀显著减轻了 H/R 应激心肌细胞中过度激活的自噬和线粒体自噬，同时上调了 SIRT3。最后，SIRT3 的敲低显著消除了西他列汀对 H/R 诱导的线粒体自噬、自噬和心肌细胞损伤的保护作用。总之，我们的数据表明，西他列汀通过介导沉默信息调节因子 3（SIRT3）和自噬来改善 H/R 诱导的心肌细胞损伤。
