Moxibustion alleviates autophagy and inhibits ferroptosis to improve cardiac function in rats with post-myocardial infarction heart failure.

Abstract

Objective: To explore the mechanism by which moxibustion alleviates autophagy and inhibits ferroptosis, thereby improving myocardial fibrosis in rats with post-myocardial infarction heart failure (post-MI HF).

Methods: We used a rat model of post-MI HF rats. Interventions included moxibustion and intraperitoneal injection of rapamycin (RAPA) along with assessing echocardiography, cardiac pathology, myocardial mitochondrial morphology, co-immunofluorescence, transmission electron microscope, Western blotting, and reverse transcriptase-quantitative polymerase chain reaction.

Results: Moxibustion improves the left ventricular ejection fraction and fractional shortening, myocardial cell morphology, and myocardial fibrosis levels induced by post-MI HF. In addition, it reduces the immunofluorescence co-localization intensity of nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1A/1B light chain 3 and decreases the level of intracellular free iron. It suppresses autophagy and ferroptosis-related indicators, downregulates NCOA4 expression, upregulates glutathione peroxidase 4 expression, and decreases lipid peroxidation levels. The activation of autophagy increases NCOA4 expression and promotes ferroptosis. Furthermore, moxibustion counteracts the effects of RAPA.

Conclusions: Moxibustion can alleviate myocardial fibrosis and exert cardioprotective effects by regulating autophagy and inhibiting ferroptosis. Our findings indicate that targeting autophagy-induced ferroptosis may serve as a novel therapeutic approach for the treatment of post-MI HF.