Cardiac energy metabolic disorder and gut microbiota imbalance: a study on the therapeutic potential of Shenfu Injection in rats with heart failure.

Abstract

Objective: To investigate the relationship between heart failure (HF) and gut microbiota-mediated energy metabolism, and to explore the role of Shenfu Injection in this process.

Materials and methods: In this study, Adriamycin-induced chronic heart failure (CHF) rat model was used and randomly divided into the blank control group (Normal, n = 9), HF control group (Model, n = 12), Shenfu Injection treatment group (SFI, n = 9), and positive drug control group (TMZ, n = 9). The changes in gut microbiota structure were analyzed by 16S rRNA high-throughput sequencing, the content of short-chain fatty acids (SCFAs) was detected by targeted metabolomics technology, and cardiac function and energy metabolism-related indicators were evaluated.

Results: Myocardial energy metabolism in HF rats was disordered, characterized by reduced fatty acid oxidation, enhanced anaerobic glycolysis of glucose, mitochondrial damage, and decreased ATP content; The gut microbiota of HF rats was imbalanced, with a reduction in beneficial bacteria, an increase in conditional pathogenic bacteria, and impaired intestinal barrier function; Both Shenfu Injection and trimetazidine improved myocardial energy metabolism and cardiac function, but Shenfu Injection was more significant in regulating gut microbiota and improving intestinal health; The production of SCFAs from the gut microbiota of HF rats increased, which may be closely related to myocardial energy metabolism; SCFAs-producing bacteria Akkermansia and Blautia played a key role in the development of HF, and their abundance was positively correlated with SCFAs content.

Conclusion: Shenfu Injection in treating HF may improve myocardial energy metabolism and intestinal health by regulating gut microbiota, especially the abundance of SCFAs-producing bacteria Akkermansia and Blautia, thereby exerting therapeutic effects. This provides theoretical support for treatment strategies based on gut microbiota.