Pathological Process Observation and Non-targeted Metabolomics Analysis of Heart Failure Rat Model Established by Transverse Aortic Constriction
10.13422/j.cnki.syfjx.20211775
- VernacularTitle:主动脉弓缩窄术建立心力衰竭大鼠模型的病理过程观察与非靶向代谢组学分析
- Author:
Sen-jie ZHONG
1
;
Xia-jun XIONG
1
;
Qian ZHANG
1
;
Si-yuan HU
1
;
Meng YANG
1
;
Shu-min HUANG
1
;
Ge FANG
1
;
Zi-yi WANG
1
;
Zhi-xi HU
1
;
Lin LI
1
Author Information
1. Institute of Traditional Chinese Medicine Diagnosis， Hunan University of Chinese Medicine，Changsha 410208，China
- Publication Type:Journal Article
- Keywords:
transverse aortic constriction （TAC）;
myocardial hypertrophy;
chronic heart failure;
metabolomics;
liquid chromatography-mass spectrometry technology;
biomarkers;
metabolic pathways
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(9):117-124
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the pathological process and changes of metabolites in myocardial tissue of heart failure induced by transverse aortic constriction （TAC） in rats. MethodRats were treated with TAC operation and divided into TAC-30 d group and TAC-60 d group， and sham operation group at the same period was set up as control. Echocardiography and pathological staining of myocardial tissue were performed on rats in each group. Enzyme-linked immunosorbent assay was used to determine the expression of amino-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum. Liquid chromatography-mass spectrometry was used to observe the changes of metabolites and related pathways in myocardial tissue， the mobile phase consisted of 25 mmol·L-1 ammonium acetate and 25 mmol·L-1 ammonia hydroxide in water （A） and acetonitrile （B） for gradient elution （0-0.5 min， 95%B； 0.5-7 min， 95%-65%B； 7-8 min， 65%-40%B； 8-9 min， 40%B； 9-9.1 min， 40%-95%B； 9.1-12 min， 95%B）， electrospray ionization was used under positive and negative ion detection modes， acquisition range was m/z 70-1 050. ResultCompared with the sham-30 d group， the left ventricular internal diameter at end-systole （LVIDs） in TAC-30 d group was significantly decreased （P<0.01）， and left ventricular ejection fraction （LVEF）， fraction shortening （FS）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left vebtricular end-systolic posterior wall thickness （LVPWs） were significantly increased （P<0.01）， there were cardiomyocyte arrangement disorder， edema， collagen fibre hyperplasia， the content of NT-probNP was significantly increased， while the content of ATP was significantly decreased （P<0.01）， and 15 metabolites with abnormal expression were involved in pyrimidine metabolic pathway， pantothenic acid and coenzyme A biosynthesis pathway. Compared with the sham-60 d group， LVEF and FS in the TAC-60 d group were significantly decreased （P<0.01）， and left ventricular internal diameter at end-diastole （LVIDd）， LVIDs and LVPWd were increased （P<0.05， P<0.01）， the edema of myocardial cells increased obviously， myocardium fibers degenerated， coagulation necrosis appeared， and a large amount of collagen fibers were deposited， the expression of NT-proBNP increased and the expression of ATP decreased （P<0.01）， there were 21 metabolites with abnormal expression， involving pyrimidine metabolic pathway， and starch and sucrose metabolic pathway. ConclusionAt 30 d after TAC， there are myocardial hypertrophy， lipid metabolism disorder， pyrimidine metabolism disorder and energy imbalance. At 60 d after TAC， there are heart failure， aggravation of lipid metabolism disorder， excessive activation of glucose metabolism， and continuous disorder of pyrimidine metabolism.
