Department of Geriatric, Wujiang District No. 1 People's Hospital, Suzhou, Jiangsu 215200, P.R. China.
Central Laboratory of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3722-3734. doi: 10.3892/mmr.2018.8371. Epub 2018 Jan 2.
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways. Mechanistically, liraglutide elevated the expression of NAD‑dependent protein deacetylase sirtuin‑1 (SIRT1), which increased the expression of Parkin, leading to mitophagy activation. Protective mitophagy reversed cellular adenosine 5'‑triphosphate production, reduced cellular oxidative stress and balanced the redox response, sustaining mitochondrial homeostasis. Notably, following blockade of glucagon‑like peptide 1 receptor or knockdown of Parkin, the beneficial effects of liraglutide on mitochondria disappeared. In conclusion, the results of the present study illustrated the protective role of liraglutide in repairing the infarcted heart via regulation of the SIRT1/Parkin/mitophagy pathway.
利拉鲁肽是一种胰高血糖素样肽-1 受体激动剂，用于治疗 2 型糖尿病患者。本研究旨在探讨利拉鲁肽在心肌梗死后修复梗死心脏中的作用和机制。本研究的结果表明，利拉鲁肽剂量增加约 28 天可减少梗死后心脏中的心肌纤维化、炎症反应和心肌死亡。在体外，利拉鲁肽可保护心肌细胞线粒体免受慢性缺氧损伤，抑制线粒体凋亡途径。在机制上，利拉鲁肽上调了烟酰胺腺嘌呤二核苷酸（NAD）依赖性蛋白去乙酰化酶 SIRT1 的表达，增加了 Parkin 的表达，从而激活自噬。保护性自噬可逆转细胞三磷酸腺苷的产生，减少细胞氧化应激并平衡氧化还原反应，维持线粒体的动态平衡。值得注意的是，阻断胰高血糖素样肽 1 受体或敲低 Parkin 后，利拉鲁肽对线粒体的有益作用消失。综上所述，本研究结果表明，利拉鲁肽通过调节 SIRT1/Parkin/自噬通路在修复梗死心脏中发挥保护作用。
