Exploring The Potential Biomarkers And Biological Basis Of Urine In Patients With Heart Qi Deficiency Syndrome In Coronary Heart Disease Based On Non-targeted Metabolomic

Objective:(1)To study the characteristics of urine metabolomics in coronary heart disease(CHD)rats with heart-qi deficiency syndrome,explore potential biomarkers,and provide experimental basis for clinical diagnosis and treatment of heart-qi deficiency syndrome in CHD,explore the essence and scientific connotation of syndromes.(2)To establish the TCM and western medicine intervention models of Yangxin Tongmai formula and metoprolol tartrate intervention groups,then analyze the differences between the effects of two drugs on urine metabolites in CHD rats with heart-qi deficiency syndrome.Through the databases to find possible metabolic pathways,further explore the material basis and objective indicators of syndrome differentiation.To elucidate the multifactorial regulation of TCM syndromes of CHD at the molecular level.Methods: The experimental animals were divided into healthy blank control group,CHD heart-qi deficiency syndrome model group,Yangxin Tongmai formula intervention group and metoprolol tartrate intervention group.After model validation,the TCM and western medicine groups were given Yangxin Tongmai formula and metoprolol tartrate suspension by gavage for 14 days.After urine samples were collected from each group,untargeted metabolites were detected by ultra performance liquid chromatography-mass spectrometry(UPLCMS),differential metabolites were identified using multivariate statistics and univariate statistics,and potential biomarkers were screened.Differential metabolic pathways and the most relevant pathways were sought by KEGG analysis,MSEA analysis,topology analysis and trend analysis.Results:(1)Urine metabolomics in the CHD heart-qi deficiency syndrome model group: 249 differential metabolites were identified,28 substances were upregulated and 221 substances were downregulated.3 potential biomarkers:pyridoxine,N1-methyl-2-pyridone-5-carboxamide,phenylpyruvic acid.The 4most relevant metabolic pathways: vitamin B6 metabolism,nicotinate and nicotinamide metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabolism.(2)Urine metabolomics in the Yangxin Tongmai formula intervention group:20 differential metabolites were identified,12 substances were upregulated and8 substances were downregulated.2 potential biomarkers: 6-phosphogluconic acid,uracil.The 2 most relevant metabolic pathways: pentose phosphate pathway,pyrimidine metabolism.(3)Urine metabolomics in the metoprolol tartrate intervention group: 37 differential metabolites were identified,32 substances were upregulated and 5substances were downregulated.3 potential biomarkers: L-glutamine,N1-methyl-2-pyridone-5-carboxamide,uracil.The 3 most relevant metabolic pathways: alanine,aspartate and glutamate metabolism,nicotinate and nicotinamide metabolism,pyrimidine metabolism.Conclusion:(1)The 3 small molecule compounds can be used as potential biomarkers for the heart-qi deficiency syndrome model of CHD,which are related to metabolism of cofactors and vitamins,amino acid metabolism,carbohydrate metabolism.(2)Intervention of the heart-qi deficiency syndrome by Yangxin Tongmai formula can correct the tendency of 2 abnormal metabolites,and their therapeutic mechanisms may be related to carbohydrate metabolism,nucleotide metabolism.(3)Metoprolol tartrate can correct the tendency of 3 abnormal metabo lites when intervening in heart-qi deficiency syndrome,and its therapeutic mechanism may be related to amino acid metabolism,metabolism of cofactors and vitamins,nucleotide metabolism.