School of Medicine, Nankai University, Tianjin 300071, China; Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
School of Medicine, Nankai University, Tianjin 300071, China; Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
Int Immunopharmacol. 2023 Aug;121:110435. doi: 10.1016/j.intimp.2023.110435. Epub 2023 Jun 13.
Myocardial infarction (MI) is a serious cardiovascular disease with a poor prognosis. Macrophages are the predominant immune cells in patients with MI and macrophage regulation during the different phases of MI has important consequences for cardiac recovery. Alpha-lipoic acid (ALA) plays a critical role in MI by modulating the number of cardiomyocytes and macrophages.
MI mice were generated by ligating the left anterior descending coronary artery. Macrophages were exposed to hypoxia to establish a hypoxia model and M1 polarization was induced by LPS and IFN-γ. Different groups of macrophages and MI mice were treated with ALA. The cardiomyocytes were treated with various macrophage supernatants and the cardiac function, cytokine levels, and pathology were also analyzed. Factors related to apoptosis, autophagy, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) were assessed. Finally, the HMGB1/NF-κB pathway was identified.
ALA promoted M2b polarization in normal cells and suppressed inflammatory cytokines during hypoxia. ALA inhibited ROS and MMP production in vitro. Supernatants containing ALA inhibited apoptosis and autophagy in hypoxic cardiomyocytes. Moreover, ALA suppressed the HMGB1/NF-κB pathway in macrophages, which may be a potential mechanism for attenuating MI.
ALA alleviates MI and induces M2b polarization via the HMGB1/NF-κB pathway, impeding inflammation, oxidation, apoptosis, and autophagy, and might be a potential strategy for MI treatment.
心肌梗死（MI）是一种预后不良的严重心血管疾病。巨噬细胞是 MI 患者中主要的免疫细胞，巨噬细胞在 MI 的不同阶段的调节对心脏恢复有重要影响。α-硫辛酸（ALA）通过调节心肌细胞和巨噬细胞的数量在 MI 中发挥关键作用。
通过结扎左前降支冠状动脉来建立 MI 小鼠模型。将巨噬细胞暴露于缺氧环境中以建立缺氧模型，并通过 LPS 和 IFN-γ诱导 M1 极化。用 ALA 处理不同组别的巨噬细胞和 MI 小鼠。用各种巨噬细胞上清液处理心肌细胞，并分析心脏功能、细胞因子水平和病理情况。评估与细胞凋亡、自噬、活性氧（ROS）和线粒体膜电位（MMP）相关的因素。最后，鉴定了 HMGB1/NF-κB 通路。
ALA 促进正常细胞中的 M2b 极化，并在缺氧时抑制炎症细胞因子的产生。ALA 抑制体外 ROS 和 MMP 的产生。含有 ALA 的上清液抑制缺氧心肌细胞中的细胞凋亡和自噬。此外，ALA 抑制巨噬细胞中的 HMGB1/NF-κB 通路，这可能是减轻 MI 的潜在机制。
ALA 通过 HMGB1/NF-κB 通路缓解 MI 并诱导 M2b 极化，抑制炎症、氧化、细胞凋亡和自噬，可能是 MI 治疗的一种潜在策略。
