Qu Xiaolong, Yang Pan, Jiao Li, Yin Yuehui
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, 401336 Chongqing, China.
Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University, 400038 Chongqing, China.
Front Biosci (Landmark Ed). 2025 Jan 20;30(1):25565. doi: 10.31083/FBL25565.
Myocardial ischemia-reperfusion (I/R) injury and coronary microcirculation dysfunction (CMD) are observed in patients with myocardial infarction after vascular recanalization. The antianginal drug trimetazidine has been demonstrated to exert a protective effect in myocardial ischemia-reperfusion injury.
This study aimed to investigate the role of trimetazidine in endothelial cell dysfunction caused by myocardial I/R injury and thus improve coronary microcirculation.
The myocardial I/R mouse model was established, and trimetazidine was administered for 7 days before myocardial I/R model establishment. Echocardiography, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, and thioflavin S staining were applied to assess myocardial injury and microvascular function. Additionally, the oxygen-glucose deprivation/reperfusion (OGD/R) model was developed in endothelial cells to simulate myocardial I/R injury . Griess reaction method, immunofluorescence, and western blotting (WB) were employed to detect the expressions of nitric oxide (NO), platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial (VE)-cadherin, zonula occludens protein 1 (ZO-1), occludin, vascular endothelial growth factor (VEGF) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling-related proteins in endothelial cells and mouse cardiomyocytes. AMPK pathway inhibitor compound C was used for further mechanism validation.
Our research demonstrated that trimetazidine can alleviate myocardial pathological injury and cardiac function injury during myocardial I/R. Trimetazidine was observed to improve microvascular reflux phenomenon and microvascular function and barrier injury in myocardial I/R and OGD/R models. Additionally, the expressions of AMPK signal-related proteins were found to be inhibited in myocardial I/R and OGD/R models, which were then activated in mice administered trimetazidine. However, the effects of trimetazidine on endothelial cell function and barrier damage were attenuated after co-treatment with compound C and trimetazidine.
Trimetazidine ameliorated myocardial I/R-induced CMD by activating AMPK signaling.
在血管再通后的心肌梗死患者中观察到心肌缺血再灌注（I/R）损伤和冠状动脉微循环功能障碍（CMD）。抗心绞痛药物曲美他嗪已被证明对心肌缺血再灌注损伤具有保护作用。
本研究旨在探讨曲美他嗪在心肌I/R损伤所致内皮细胞功能障碍中的作用，从而改善冠状动脉微循环。
建立心肌I/R小鼠模型，并在建立心肌I/R模型前7天给予曲美他嗪。应用超声心动图、2,3,5-三苯基四氮唑氯化物（TTC）染色、苏木精-伊红（H&E）染色和硫黄素S染色评估心肌损伤和微血管功能。此外，在内皮细胞中建立氧糖剥夺/再灌注（OGD/R）模型以模拟心肌I/R损伤。采用Griess反应法、免疫荧光和蛋白质印迹法（WB）检测内皮细胞和小鼠心肌细胞中一氧化氮（NO）、血小板内皮细胞黏附分子-1（CD31）和血管内皮（VE）-钙黏蛋白、闭锁小带蛋白1（ZO-1）、闭合蛋白、血管内皮生长因子（VEGF）和腺苷单磷酸（AMP）激活的蛋白激酶（AMPK）信号相关蛋白的表达。使用AMPK通路抑制剂化合物C进行进一步的机制验证。
我们的研究表明，曲美他嗪可减轻心肌I/R期间的心肌病理损伤和心脏功能损伤。观察到曲美他嗪可改善心肌I/R和OGD/R模型中的微血管反流现象、微血管功能及屏障损伤。此外，在心肌I/R和OGD/R模型中发现AMPK信号相关蛋白的表达受到抑制，而在给予曲美他嗪的小鼠中这些蛋白被激活。然而，在化合物C与曲美他嗪联合处理后，曲美他嗪对内皮细胞功能和屏障损伤的作用减弱。
曲美他嗪通过激活AMPK信号改善心肌I/R诱导的CMD。
