Study On Plasmatic Metabolites Of Septic Rats Based On Metabonomics

Objective:Sepsis is a physiological and biochemical response imbalance initiated by infection,which can develop into organ dysfunction or even death.Metabolic disorders often occur in patients with sepsis,which could induce immune dysfunction,multiple organ dysfunction syndrome(MODS) and death.In the present study,the Gas Chromatography-Mass Spectrometry(GC-MS) is used to determine the plasma samples of septic rats,validate the changes of plasma metabolites during sepsis,and find the potential biomarkers so as to provide new useful indicators for early diagnosis of sepsis and basis for future studies.Methods:In this study,rat sepsis model is firstly established by cecal ligation and puncture(CLP) and validated by the survival rate of the septic rats,inflammatory factors(such as IL-6,TNF-?,etc.) using enzyme-linked immunosorbent assay(ELISA) and pathological changes of liver,lung and kidney by HE staining.6h after operation,plasma samples of rats are collected and measure through GC-MS for metabolomics analysis,which help us to identify the changes of plasma metabolites in sepsis.Results:1.The rat sepsis model is established by cecal ligation and puncture(CLP).ELISA shows that the concentrations of TNF-? and IL-6 increase in the serum of sepsis rats,and HE staining shows that liver,lung and kidney tissue of sepsis rats occured injure,which suggests that the sepsis model is established successfully2.Some results can be found after metabolic research: The plasma metabolites of sepsis rats are significantly changed after 6h since modeling.By analyzing and comparing the differences in plasma metabolites between the sepsis group and the sham group,27 metabolites related to sepsis are observed as follows: phthalate acid,5-hydroxyindole-2-carboxylic acid,ribose,5-aminovaleric acid,glucose,3-phosphoglycerate,3-hydroxy-aminobenzoic acid,2-hydroxyvaleric acid,allo-inositol,6-hydroxyacetic acid dimer,2-deoxycytidonic acid,4-vinylphenol dimer,guanidine succinic acid,3-cyanalanine,sedoheptulose,3-hydroxypyridine,levoglucosan,benzoin,DL-dihydrosphingosine,thioctamide,2-hydroxypyridine,arachidonic acid,saccharic acid,N-carbamylglutanmte,putrescine,2-deoxy-D-galactose,ethyl cinnamate.3.The biological and chemical analysis of the 27 different metabolites mentioned above are conducted.Furthermore,the path diagram for sepsis metabolism is obtained through accessing to relevant literature and related databases.From the diagram it can be observed that sepsis can cause amino acids,sugars,fats and other metabolic disorders,which are related to energy metabolism,inflammatory response and oxidative stress.Conclusions:27 metabolites related to sepsis are identified in present study.After analysis of these related metabolites,we can know that sepsis is mainly related to carbohydrate metabolism disorders,amino acid metabolic disorders,lipid metabolism disorders,etc.These metabolic disorders mentioned above are related to energy metabolism,inflammatory response and oxidative stress.