[Effect of Trichosanthis Pericarpium extract on bile acid metabolism in coronary heart disease model rats].

This study aims to explore the potential mechanism of action of Trichosanthis Pericarpium(TP) in improving coronary heart disease(CHD) based on a CHD rat model and metabolomics. The rat model of CHD was built by subcutaneous injection of high-fat diet combined with isoprenaline hydrochloride(ISO). To compare the expression level of lactate dehydrogenase, cardiac troponin Ⅰ(cTnⅠ), creatine kinase-MB(CK-MB), creatine kinase(CK), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β),interleukin-6(IL-16), hypersensitive C-reactive protein(hs-CRP) in serum and cardiac pathological changes of model animals after administration of TP, LTQ-Orbitrap-MS analysis was combined with principal component analysis. The effect of TP on endogenous metabolites in the feces of CHD rats was studied. In addition, biomarkers were identified using the HMDB database and metabolic pathway enrichment analysis was performed using the MetaboAnalyst online pathway enrichment tool. The content of bile acid was further determined in the feces and serum of different groups of rats. Compared with blank group, the myocardial injury markers(CK,LDH, cTnⅠ, CK-MB) and inflammatory factors(TNF-α, IL-1β, IL-6, hs-CRP) in serum of CHD rats were significantly increased.Myocardial injury and inflammatory infiltration in CHD rats were significantly improved by TP extract. The primary bile acid biosynthetic metabolism pathway was enriched by non-targeted metabolome analysis. The levels of total bile acid, primary bile acid,secondary bile acid, and unconjugated bile acids in the feces of CHD rats were significantly lower than those of control rats. Fecal excretion of total bile acid, primary bile acid, and unconjugated bile acid was significantly improved by TP extract. The levels of total bile acid, primary bile acid, secondary bile acid, and unconjugated bile acids in the serum of CHD rats were significantly higher than those of control rats. Circulating blood levels of total bile acids, primary bile acids, secondary bile acids, and unconjugated bile acids were significantly reduced by TP extract. Increasing fecal excretion of bile acid and decreasing the level of bile acid in blood circulation can improve CHD, and maintaining proper bile acid metabolism is one of the mechanisms of TP to improve CHD.