Luhong Granules Prevent Ventricular Remodelling after Myocardial Infarction by Reducing the Metabolites TMAO and LPS of the Intestinal Flora.

Abstract

Background Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. Purpose In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. Methods Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg−1·d−1), vancomycin (0.075 g·ml−1·d−1), and 0.9% saline (5 ml·kg−1·d−1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). Results H&E and Masson's trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P < 0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P < 0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P < 0.05). Conclusions Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.