Metabolomics approach based on utra-performance liquid chromatography coupled to mass spectrometry with chemometrics methods for high-throughput analysis of metabolite biomarkers to explore the abnormal metabolic pathways associated with myocardial dysfunction.

Abstract

Ultra-performance liquid chromatography/mass spectrometry-based metabolomics can been used for discovery of metabolite biomarkers to explore the metabolic pathway of diseases. Identification of metabolic pathways is key to understanding the pathogenesis and mechanism of disease. Myocardial dysfunction induced by sepsis (SMD) is a severe complication of septic shock and represents major causes of death in intensive care units; however its pathological mechanism is still not clear. In this study, ultrahigh-pressure liquid chromatography with mass spectrometry-based metabolomics with chemometrics anaylsis and multivariate pattern recognition analysis were used to detect urinary metabolic profile changes in a lipopolysaccharide-induced SMD mouse model. Multivariate statistical analysis including principal component analysis and orthogonapartial least squares discriminant analysis for the discrimination of SMD was conducted to identify potential biomarkers. A total of 19 differential metabolites were discovered by high-resolution mass spectrometry-based urinary metabolomics strategy. The altered biochemical pathways based on these metabolites showed that tyrosine metabolism, phenylalanine metabolism, ubiquinone biosynthesis and vitamin B6 metabolism were closely connected to the pathological processes of SMD. Consequently, integrated chemometric analyses of these metabolic pathways are necessary to extract information for the discovery of novel insights into the pathogenesis of disease.