AIM  To investigate the cardioprotective effects of electroacupuncture (EA) at the Neiguan acupoint (PC6) against myocardial ischemia-reperfusion injury (MI/RI) in mice and explore the underlying metabolic mechanisms using metabolomics.

METHODS  Mice were randomly assigned to four groups: ① Sham (thoracotomy without ligation), ②MI/RI (ischemia-reperfusion model), ③ PC6+Sham (EA at PC6 without MI/RI), and ④ PC6+MI/RI (EA preconditioning + MI/RI). The PC6+Sham and PC6+MI/RI groups received EA at PC6 for 7 consecutive days before modeling. The MI/RI model was induced by left anterior descending coronary artery ligation, followed by reperfusion. Cardiac function was assessed via echocardiography, and myocardial injury was evaluated by infarct size (Evans blue/TTC dual staining), myocardial injury marker enzyme levels (ELISA), and myocardial tissue metabolites (LC-MS/MS). Multivariate statistical analyses (PCA/OPLS-DA) were used to identify differential metabolites and enriched metabolic pathways.

RESULTS  EA preconditioning at PC6 significantly improved cardiac function, reduced infarct size, and attenuated serum biomarker elevations (P<0.05 or P<0.01). Metabolomic analysis revealed distinct metabolic profiles between the MI/RI and Sham groups, identifying 187 candidate differential metabolites (e.g., ADP) and enriched pathways, including D-amino acid metabolism. Compared to MI/RI alone, the PC6+MI/RI group exhibited a distinct metabolic profile, with 82 candidate differential metabolites (e.g., upregulated creatine, downregulated lactate) and significant pathway enrichment (e.g., protein digestion and absorption).

CONCLUSION  EA preconditioning at PC6 mitigates MI/RI progression. Its protective mechanism may be associated with the regulation of metabolic pathways such as protein digestion and absorption. Metabolomic analysis revealed differential metabolites such as L-serine may serve as potential biomarkers for EA’s cardioprotective effects against MI/RI.