Protective effect of exercise induced metabolite-3 in ischemia-reperfusion injury
10.12025/j.issn.1008-6358.2025.20250279
- VernacularTitle:运动后分泌代谢物3对心肌细胞缺血再灌注损伤的保护作用
- Author:
Zijie CHENG
1
;
Xuejun WANG
1
;
Zimu WANG
1
;
Juying QIAN
1
Author Information
1. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, National Health Commission Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
- Publication Type:Originalarticle
- Keywords:
myocardial infarction;
ischemia-reperfusion injury;
metabolomics
- From:
Chinese Journal of Clinical Medicine
2025;32(3):403-409
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the protective effect of exercise-induced metabolite-3 (EIM-3) on myocardial ischemia-reperfusion (I/R) injury and explore its underlying molecular mechanisms. Methods The physicochemical properties and half-life of EIM-3 were analyzed using the Human Metabolome Database (HMDB, https://hmdb.ca/). A primary rat cardiomyocyte hypoxia/reoxygenation (H/R) injury model was established. Cell apoptosis and viability were assessed using TUNEL assay and cell counting kit-8, respectively. Lactate dehydrogenase (LDH) levels in the cell culture supernatant were measured. Intracellular reactive oxygen species (ROS) levels were detected. Transcriptomic analysis was performed to identify potential signaling pathways and targets of EIM-3. Results Plasma levels of EIM-3 were elevated post-exercise. EIM-3 was characterized as a phospholipid small-molecule compound with a partition coefficient (logP) of 5.58 and a solubility (logS) of −7.6, indicating favorable lipophilicity and cell membrane permeability. In cardiomyocytes H/R injury modles, EIM-3 significantly inhibited apoptosis, increased cell viability, reduced intracellular ROS levels, and decreased LDH release (P＜0.01). Transcriptomic analysis suggested that EIM-3 exerts its protective function potentially by regulating glucose metabolim. Quantitative real-time polymerase chain reaction results confirmed that EIM-3 significantly upregulated the transcriptional level of pyruvate kinase M2 (PKM2) in a dose-dependent manner (P＜0.001). Conclusions EIM-3 protects cardiomyocytes against I/R injury by modulating glucose metabolim. This study provides foundational insights into the mechanisms underlying exercise-induced cardioprotection.
