Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People's Republic of China.
Clin Exp Immunol. 2023 Apr 7;212(1):61-69. doi: 10.1093/cei/uxad016.
Reperfusion after acute myocardial infarction can cause ischemia/reperfusion (I/R) injury, which not only impedes restoration of the functions of tissues and organs but may also aggravate structural tissue and organ damage and dysfunction, worsening the patient's condition. Thus, the mechanisms that underpin myocardial I/R injury need to be better understood. We aimed to examine the effect of dexmedetomidine on macrophage migration inhibitory factor (MIF) in cardiomyocytes from mice with myocardial I/R injury and to explore the mechanistic role of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling in this process. Myocardial I/R injury was induced in mice. The expression of serum inflammatory factors, reactive oxygen species (ROS), adenosine triphosphate (ATP), and AMPK pathway-related proteins, as well as myocardial tissue structure and cell apoptosis rate, were compared between mice with I/R injury only; mice with I/R injury treated with dexmedetomidine, ISO-1 (MIF inhibitor), or both; and sham-operated mice. Dexmedetomidine reduced serum interleukin (IL)-6 and tumor necrosis factor-α concentrations and increased IL-10 concentration in mice with I/R injury. Moreover, dexmedetomidine reduced myocardial tissue ROS content and apoptosis rate and increased ATP content and MIF expression. MIF inhibition using ISO-1 reversed the protective effect of dexmedetomidine on myocardial I/R injury and reduced AMPK phosphorylation. Dexmedetomidine reduces the inflammatory response in mice with I/R injury and improves adverse symptoms, and its mechanism of action may be related to the MIF-AMPK pathway.
急性心肌梗死后再灌注会引起缺血/再灌注（I/R）损伤，不仅会阻碍组织和器官功能的恢复，还可能加重结构组织和器官损伤及功能障碍，使患者病情恶化。因此，需要更好地了解导致心肌 I/R 损伤的机制。本研究旨在探讨右美托咪定对心肌 I/R 损伤小鼠心肌细胞中迁移抑制因子（MIF）的影响，并探讨腺苷 5'-单磷酸激活蛋白激酶（AMPK）信号通路在此过程中的作用机制。采用小鼠心肌 I/R 损伤模型，比较 I/R 损伤组、右美托咪定组、ISO-1（MIF 抑制剂）组、右美托咪定+ISO-1 组及假手术组小鼠血清炎症因子、活性氧（ROS）、三磷酸腺苷（ATP）、AMPK 通路相关蛋白表达以及心肌组织形态学和细胞凋亡率的差异。结果显示，与 I/R 损伤组相比，右美托咪定组小鼠血清白细胞介素（IL）-6 和肿瘤坏死因子-α浓度降低，IL-10 浓度升高，心肌组织 ROS 含量和细胞凋亡率降低，ATP 含量和 MIF 表达升高。ISO-1 抑制 MIF 表达可逆转右美托咪定对心肌 I/R 损伤的保护作用，并降低 AMPK 磷酸化水平。右美托咪定减轻了 I/R 损伤小鼠的炎症反应，改善了不良症状，其作用机制可能与 MIF-AMPK 通路有关。
