Based On LC-MS Technology To Explore The Intervention Mechanism Of Urinary Metabolites Of Hypertension, Heart Failure And Deficiency Of Heart-qi And Yin And Shenmai Injection

Objective:(1)To research the characteristics of urine metabolomics in rats with Heart-Qi-Yin deficiency syndrome of hypertensive heart failure,and to search for potential differential metabolites,so as to provide experimental basis for clinical diagnosis and treatment of heart failure.(2)To research the effect of Shenmai injection on urine metabolomics in hypertensive heart failure,and to explore the mechanism of Shenmai injection in treating heart failure from small molecular metabolites,so as to lay the foundation for clinical application of traditional Chinese medicine.Methods:Twenty Dahl / SS salt-sensitive rats were randomly divided into normal group(6)and model group(14).Rats in the normal group were given a lowsalt diet(0.3% Na Cl),and rats in the model group were fed with 8% Na Cl for20 weeks.According to the method of random number table,14 rats were divided into model group(7)and Shenmai injection group(7).Shenmai injection group was administrated by intraperitoneal injection,the model group was given sterile water for injection.After 15 days of administration,urine samples of rats in normal group,model group and Shenmai injection group were collected by using the metabolic cages,it was examined by liquid chromatography-mass spectrometry(LC-MS),and used multivariate statistical methods(principal component analysis,partial least squares analysis,etc.)to find differential metabolites.Screen for differential metabolic pathways with Metabo Analyst online analysis software.Results:(1)Urine metabolomics in rats with hypertensive heart failure :There were significant differences in the metabolic characteristics of urine in the model group and the normal group,25 kinds of metabolites including lipids,amino acids,sugars,etc.15 metabolic pathways were detected.Compared with the normal group,the creatine,inositol,nicotinic acid,uridine,cis-aconitic acid,1-methylhistidine,L-arginine,kynuric acid,4-pyridine acidand other substances in the model group dropped;the pantothenic acid,3-dehydroquinic acid,5-l-glutaryl-taurine and other substances in the model group increased.it involved arginine and proline metabolism,pantothenic acid and acetyl-Co A biosynthesis and tricarboxylic acid cycle Changes in metabolic pathways.(2)Effect of Shenmai Injection on urine metabonomics in hypertensive heart failure rats : There were significant differences in the metabolic characteristics of urine in three groups of rats.Six statistically significant metabolites,which included lipids,amino acids and so on,and 10 metabolic pathways were detected.Compared with the model group,the concentrations of L-arginine,creatine,inositol,4-pyridine,kynuric acid,and5-L-glutamyl-taurine in the Shenmai injection group significantly retreated to the normal direction.It mainly involved changes in metabolic pathways such as arginine and proline metabolism,and inositol phosphate metabolism.Conclusions:(1)25 kinds of small molecular metabolites can be used as different metabolites in rats with Heart-Qi-Yin deficiency syndrome of hypertensive heart failure.Different metabolites are related to energy metabolism,amino acid metabolism,sugar metabolism,lipid metabolism and purine metabolism.(2)The intervention of Shenmai injection in hypertensive heart failure rats can make abnormal metabolites tend to normal.The mechanism of its treatment for heart failure may be related to regulating amino acid metabolism,energy metabolism and oxidative stress.