Exploration on Syndrome Types and Metabolic Markers of Rat Model with Heart Failure Caused by Transverse Aortic Constriction Based on Theory of Correspondence of Prescription and Syndrome / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine （TCM） injections on rat model of heart failure induced by transverse aortic constriction （TAC）， explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome， and reveal the biological basis of prescription-syndrome from the perspective of metabolism. MethodRats were treated with TAC for modeling and were divided into Shenmai injection group （6.0 mL·kg-1）， model group， Danhong injection group （6.0 mL·kg-1）， Shenfu injection group （6.0 mL·kg-1） and trimetazidine group （10 mg·kg-1）， and sham operation group was set up as control. After drug intervention for 15 days， echocardiography， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and myocardial histopathological staining were performed for each group， so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection， and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue. ResultCompared with the sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （FS） in the model group decreased （P<0.01）， while the left ventricular end-diastolic diameter （LVIDd）， left ventricular internal diameter at end-systole （LVIDs） and NT-proBNP level increased （P<0.01）. Compared with model group， LVEF and FS increased （P<0.01）， LVIDd， LVIDs and NT-proBNP level decreased （P<0.05， P<0.01） in Danhong injection group， NT-proBNP level in Shenfu injection group decreased （P<0.05）， LVIDd and NT-proBNP level increased （P<0.05， P<0.01） in Shenmai injection group， in trimetazidine group， LVEF and FS increased （P<0.01）， while LVIDs and NT-proBNP level decreased （P<0.05， P<0.01）. Serum glucose， low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks （P<0.01， P<0.05）. There were the callback of 9 myocardial metabolites in Danhong injection group， including glycine， serine and threonine metabolism， glyoxylate and dicarboxylate metabolism， glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group， including glycerol phospholipid metabolism. ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection， suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid， glucose， amino acid and butyric acid.