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Effect and mechanism of Jiashen Prescription on chronic heart failure model rats based on metabonomics
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DOI   10.11656/j.issn.1672-1519.2022.12.14
Key Words   Jiashen Prescription;chronic heart failure;metabonomics
Author NameAffiliationE-mail
WANG Caijun Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
SONG Zhihui Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CHEN Rui Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CHEN Siyu Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
FENG Wanying Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LYU Qingbo Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
E Xiuhui Modern Chinese Medicine Development Center, Tianshili Pharmaceutical Group Co., Ltd., Tianjin 300410, China exhgame@hotmail.com 
WANG Yi Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China wangyi@tjutcm.edu.cn 
Abstract
    [Objective] Based on the efficacy of Jiashen Prescription in the treatment of chronic heart failure(CHF),to explore the mechanism of its anti-heart failure effect by metabonomics. [Methods] The CHF model was formed after myocardial infarction caused by ligation of the anterior descending branch of the left coronary artery in rats,and was administered continuously for 4 weeks. Cardiac function was detected by ultrasound,myocardial pathological changes were detected by HE staining,myocardial fibrosis was detected by Masson staining,and the level of N-terminal brain natriuretic peptide(NT-proBNP) in myocardial tissue was detected by ELISA. To explore the pharmacodynamic effect of Jiashen Prescription on CHF;Ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC—Q—TOF-MS) was used for untargeted metabolomics detection of small molecule metabolites in serum and urine of rats and multivariate statistical analysis was performed to find metabolic markers for disease occurrence. Finally,MetaboAnalyst metabolic analysis platform was used to construct the metabolic pathway of Jiashen Prescription for CHF treatment. [Results] It significantly increased left ventricular ejection fraction(EF) and short axis shortening rate(FS) in CHF rats,alleviated myocardial pathological injury and fibrosis,decreased myocardial collagen volume fraction(CVF),and decreased the level of NT-proBNP in CHF rats. The 33 metabolic markers,mainly lipids and amino acids and their derivatives,were obtained in serum of CHF rats,and 38 metabolic markers,mainly amino acids and their derivatives,long-chain fatty acids and nucleosides,were obtained in urine of CHF rats. Compared with model group,21 metabolites and 29 metabolites in serum and urine of Jiashen Prescription group showed a callback trend,respectively. Jiashen Prescription mainly interferes with serum metabolic markers through glycerol phospholipid metabolism,sphingolipid metabolism, alanine,aspartic acid and glutamate metabolism pathways,and interferes with urine metabolic markers through pantothenic acid and CoA biosynthesis,histidine metabolism and purine metabolism pathways. [Conclusion] Jiashen Prescription can improve CHF mainly through lipid metabolism,amino acid metabolism,energy metabolism and purine metabolism pathways.

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