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Electroacupuncture pretreatment attenuates myocardial ischemia/reperfusion injury-induced ferroptosis via the p53/SLC7A11/GPX4 pathway

Year: 2026

Type: article

Abstract: Introduction: A major side effect of reperfusion therapy after myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture (EA) preconditioning has a long history of application in the treatment of cardiovascular diseases. This study aims to investigate whether EA preconditioning alleviates MIRI by regulating the p53/SLC7A11/GPX4 pathway to suppress the ferroptotic biochemical phenotype characterized by iron accumulation and lipid peroxidation. Methods: Healthy male SPF rats were randomly divided into nine groups: Ctrl, Sham, MIRI, EA, RSL-3+EA, COTI-2+EA, Erastin+EA, COTI-2+Erastin+EA, and COTI-2+Pantethine+EA. Before MIRI induction, EA pretreatment was applied daily at CV4, bilateral ST36, and bilateral PC6 for 20 min (2 Hz, 1 mA) for 7 consecutive days. Pharmacological interventions were administered intraperitoneally once daily for 7 consecutive days before EA stimulation. The MIRI model was established by ligating the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. Myocardial oxidative stress, ferroptosis-related markers, myocardial injury markers, and cardiomyocyte apoptosis were assessed using corresponding commercial kits, DCFH-DA probe combined with flow cytometry, RhoNox-6 fluorescent probe, Western blot, RT-PCR, ELISA, and TUNEL staining combined with flow cytometry. Results: EA preconditioning inhibited p53 expression, promoted the activation of the SLC7A11/GPX4 pathway, and thereby alleviated myocardial injury. The morphology of cardiomyocytes in EA-pretreated rats was altered, and the apoptosis rate of cardiomyocytes in these rats was also reduced. In addition, administration of Erastin (SLC7A11 inhibitor) showed effects similar to those of COTI-2 (p53 agonist) intervention, whereas pantethine (SLC7A11 agonist) reversed the effects of COTI-2, exerting anti-ferroptotic and cardioprotective effects. Discussion: As a proof‑of‑concept study with limited sample size per experimental group, our findings preliminarily suggest that EA preconditioning ameliorates MIRI by suppressing the ferroptotic biochemical signature characterized by myocardial iron overload and lipid peroxidation through the p53/SLC7A11/GPX4 pathway. Further studies with larger sample sizes are still needed for validation.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1928208