Electroacupuncture preconditioning alleviates myocardial ischemia-reperfusion injury through reducing the inflammatory response mediated by the miR-۱۴۶a/TRAF۶/IRAK۴ pathway

Objective(s): Myocardial ischemia-reperfusion injury (MIRI) lacks effective multi-target interventions. Electroacupuncture (EA) shows cardioprotective potential, but its molecular mechanisms remain incompletely understood. This study aimed to investigate whether EA exerts cardioprotective effects by modulating myocardial miR-۱۴۶a, a microRNA closely associated with inflammation and cardiovascular diseases. Materials and Methods: A rat model of MIRI was established, and Sprague-Dawley rats were divided into four groups: sham, MIRI, EA treatment, and miR-۱۴۶a inhibition+EA. Cardiac function, infarct size, myocardial injury, apoptosis, and inflammatory cytokine levels were assessed using echocardiography, TTC staining, CK and LDH assays, TUNEL staining, and ELISA, respectively. The expression and cellular origin of miR-۱۴۶a were assessed via qRT-PCR, in situ hybridization, and immunofluorescence.Results: EA treatment significantly improved cardiac function, reduced infarct size, attenuated myocardial injury and apoptosis, and upregulated miR-۱۴۶a expression in cardiomyocytes. In contrast, inhibition of miR-۱۴۶a markedly attenuated the protective effects of EA and down-regulated the expression of angiogenic factors bFGF and VEGF, while compromising its anti-inflammatory actions. Furthermore, EA-mediated down-regulation of the inflammatory response was mediated through the miR-۱۴۶a/TRAF۶/IRAK۴ pathway. Conclusion: These findings suggest that EA may alleviate MIRI by upregulating myocardial miR-۱۴۶a expression, providing novel molecular insights into the cardioprotective mechanisms of EA.

کلیدواژه ها:

Cardiomyocytes ، Electroacupuncture ، Inflammatory response ، miR-۱۴۶a ، Myocardial ischemic-reperfusion injury