Abstract
Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil. The results revealed that energy-substrate metabolism were significantly disturbed by ischemia-reperfusion (I/R) in myocardium and bulk of the key metabolites could be further modulated by verapamil and/or WXKL. Lipid metabolism and amino acid transamination occurred mainly following the treatment of verapamil, whereas glucose oxidation and BCAA degradation were prominently ameliorated by WXKL to content the energy demands of heart. Moreover, both WXKL and verapamil improved the secretions of taurine and ketone bodies to overcome the oxidative stress and the shortage of energy sources induced by ischemia-reperfusion.
Highlights
Ischemic heart disease has become a worldwide health problem associated with high morbidity and mortality[1]
We employ a rat model of myocardial ischemia-reperfusion injury (MIRI) and utilize metabonomics in combination with molecular biological assays to investigate the associations and differences of metabolic remodeling effects between verapamil and Wenxin Keli (WXKL), with the objective of an in-depth understanding of similar and divergent cardioprotective effects between a Western medicine and a Traditional Chinese medicine (TCM)
Compared to Sham group, MIRI group had a significant decrease in left ventricular ejection fraction (LVEF, 72.6 ± 5.40 vs. 41.46 ± 6.27, p < 0.01), left ventricular fractional shortening (LVFS, 43.03 ± 4.56 vs. 20.97 ± 3.56, p < 0.01), left ventricular end-systolic anterior wall (LVAWs, 2.58 ± 0.29 vs. 1.56 ± 0.26, p < 0.01) and ratio of E-wave to A-wave (E/A, 1.75 ± 0.17 vs. 1.33 ± 0.18, p < 0.01), whereas an increase in left ventricular end-systolic dimension (LVIDs, 3.95 ± 0.53 vs. 5.45 ± 0.86, p < 0.01) and left ventricular systolic volume (LV Vols, 69.76 ± 22.7 vs. 148.72 ± 54.39, p < 0.05)
Summary
Ischemic heart disease has become a worldwide health problem associated with high morbidity and mortality[1]. Verapamil is a calcium channel blocker that is utilized clinically to treat hypertension, angina pectoris, and cardiac arrhythmia[7, 8] It is used intra-arterially to reduce ischemia reperfusion injury, control arrhythmias, and limit myocardial ischemia size[9]. Metabonomics is a systems biology approach for understanding the metabolic alterations of living systems in response to pathophysiological stimuli via multivariate statistical analysis of biological proton nuclear magnetic resonance (1H-NMR) spectroscopic data[18] It has been extensively used in diagnosis of diseases, to screen potential biomarkers as well as to discover drug targets involved. We employ a rat model of MIRI and utilize metabonomics in combination with molecular biological assays to investigate the associations and differences of metabolic remodeling effects between verapamil and WXKL, with the objective of an in-depth understanding of similar and divergent cardioprotective effects between a Western medicine and a TCM
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