Xinshuaining preparation ameliorates doxorubicin-induced cardiac injury in heart failure rats by regulating gut microbiota.

Abstract

Heart failure (HF) has a serious impact on patients' lives and health. Gut microbiota plays an important role in the development of HF. Xinshuaining (XSN) preparation has a therapeutic effect on the HF. However, the mechanism of action of XSN in HF is still unclear. Our study aimed to explore the possible function and mechanism of XSN on HF induced by doxorubicin (DOX) in rats. DOX-induced HF rat models were prepared, grouped and treated. The ultrasound indexes of rat heart were measured before sampling, and the indexes of cardiac pathology, fibrosis degree, gut microbiota and metabolites were detected by ELISA, HE staining, Masson staining, immunohistochemistry, 16SrDNA sequencing, liquid chromatography-mass spectrometry (LC/MS) after sampling. XSN can significantly improve the cardiac function of HF rats, including increasing LVEF, LVFS, decreasing LVESD, LVESV, LVEDV levels, and at the same time, XSN can also reduce the heart weight index, reduce the cardiac histopathological damage and fibrosis. In addition, XSN can regulate the abundance and function of gut microbiota, inhibit the level of TMAO, and regulate plasma metabolites in HF rats. In conclusions, XSN improves cardiac function and delays the process of cardiac fibrosis in HF rats, and its mechanism may be related to the regulation of gut microbiota and metabolites.