Abstract
Objective: Doxorubicin (DOX) is an extensively used chemotherapeutic agent that induces cardiotoxicity. Studies have reported that exercise (EXE) can alleviate DOX-induced cardiotoxicity. Therefore, this study aimed to explore the mechanism by which EXE attenuates DOX-induced myocardial injury. Methods: In this study, cell and animal models of DOX-induced myocardial injury were constructed. The animal model was subjected to EXE intervention. Results: In this study, in vitro experiments revealed that miR-30d-5p negatively regulated polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) and that GALNT7 negatively regulated the expression of thyroid stimulating hormone receptor (TSHR). miR-30d-5p downregulated the expression of GALNT7, promoted the expression of TSHR, and promoted macrophage M1 polarization, thus aggravating cardiomyocyte injury. In vivo experiments revealed that EXE intervention significantly downregulated miR-30d-5p and TSHR expression, upregulated GALNT7, reduced inflammation, and promoted M2 macrophage polarization, thereby alleviating DOX-induced myocardial injury. In addition, overexpression of miR-30d-5p or knockdown of GALNT7 weakened the intervention effect of EXE, whereas overexpression of GALNT7 or knockdown of TSHR promoted the effect of EXE. Conclusion: EXE can modulate the miR-30d-5p/GALNT7 axis to inhibit the expression of TSHR, thereby regulating the polarization of macrophages to the M2 phenotype and ultimately alleviating DOX-induced myocardial injury, which provides new targets and strategies for the clinical treatment of myocardial injury.