Electroacupuncture at PC6 mitigates myocardial ischemia-reperfusion injury by upregulating exosomal miR-22-3p and inhibiting NLRP3 pyroptosis

Myocardial ischemia-reperfusion injury (MIRI) remains a critical challenge in reperfusion therapy for severe ischemic heart disease, often exacerbating damage after blood flow restoration. A central pathological mechanism of MIRI is NLRP3 inflammasome-mediated cardiomyocyte pyroptosis, a highly inflammatory form of programmed cell death. While electroacupuncture (EA) has shown promise in mitigating MIRI, its precise molecular targets, particularly regarding NLRP3 inflammasome inhibition and the remote signaling mechanisms via serum exosomes, have been largely undefined.

Researchers established a MIRI animal model by ligating the left anterior descending coronary artery in rats. Electroacupuncture was applied at the Neiguan (PC6) acupoint. Cardiac function, myocardial infarction area, serum myocardial enzymes, and inflammatory factors were assessed using echocardiography, Evans-TTC staining, and ELISA. Myocardial cell pathological changes were examined via H&E staining. To confirm the mechanism, the NLRP3 agonist Nigericin was applied, and Western blotting and RT-qPCR measured NLRP3-related gene and protein expression. Exosomes from MIRI rats and AMI-PCI patients (with or without EA) were isolated, followed by small RNA sequencing to identify key effector miRNAs.

Electroacupuncture (EA) at Neiguan (PC6) significantly improved cardiac function, reduced myocardial infarction area, and decreased serum myocardial enzymes and inflammatory factors in the MIRI rat model. This therapeutic effect was confirmed to involve the targeting and inhibition of NLRP3 inflammasome-mediated myocardial pyroptosis. Crucially, small RNA sequencing revealed that miR-22-3p was significantly upregulated in serum exosomes following EA treatment. Further validation demonstrated that these EA-induced serum exosomes, rich in miR-22-3p, could directly inhibit NLRP3 inflammasome-mediated cardiomyocyte pyroptosis in an in vitro hypoxia/reoxygenation model. This suggests a novel exosome-mediated remote signaling pathway.

EA treatment significantly upregulated miR-22-3p in serum exosomes, which then inhibited NLRP3 inflammasome-mediated cardiomyocyte pyroptosis.