Dynamic changes of early plasma metabonomics in sepsis rats / 中华急诊医学杂志

ABSTRACT

Objective:To determine plasma metabonomic profiles of rats with early sepsis, to find the differential metabolites and related metabolic pathways of sepsis at different time points, and to reveal the pathophysiological changes of sepsis rats in the early stage.Methods:Fifteen 8-week-old male SD rats were randomly (random number) divided into the sham operation group (S group, n=6) and sepsis group (C group, n=9). Sepsis rat model was established by cecal ligation and puncture, and rats in the sham operation group only freed the cecum but without ligation and perforation. Plasma was collected from orbital blood at 2, 6 and 12 h after modeling, and metabonomics was determined by gas chromatography-mass spectrometry (GC-MS). The endogenous metabolites were identified by comparing the standard ion fragment spectrum library of NIST database and Feihn metabonomics database. Multivariate regression analysis was carried out through MetaboAnalyst4.0, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to identify the changes of metabolites, screen the related differential metabolites ( P<0.05, fold change>1.5, VIP >1.5), and then further analyze the related metabolic pathways through KEGG. Results:The PCA and PLS-DA pattern recognition showed that there was a cluster type distribution between the sepsis group and sham operation group at each time point, as well as between sepsis group at different time points. Fourteen, 25 and 21 differential metabolites were respectively detected between S2 h/C2 h group, S6 h/C6 h group and S12 h/C12 h group. The related signal pathways of differential metabolites were starch and sucrose metabolism and galactose metabolism at 2 h; starch and sucrose metabolism, galactose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism and aminoacyl tRNA biosynthesis at 6 h; and galactose metabolism, arginine and proline metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, D-glutamine and D-glutamate metabolism, and vitamin B6 metabolism at 12 h.Conclusions:The plasma metabolites of sepsis rats in the early stage show significant dynamic differences, and the changes of plasma metabolites may be involved in the pathophysiological process of sepsis.