Metabolic Analysis Of A Rat Model Of Acute On Chronic Liver Failure Based On GC-MS Technology

Objective:The study was to understand the metabolomics of acute on chronic liver failure,and point out the direction for the physiopathology study of ACLF.In addition,new indicators for the diagnosis and evaluation of chronic acute liver failure were explored to change the clinical dilemma of relying on biochemical parameters,so as to provide new possible biomarkers for the diagnosis and evaluation of ACLF.Method:SD rats with BDL were made by ligation of bile duct and the ACLF model were induced by D-galactosamine.Rats were sacrificed at different time points(Oh,24h,36h,48h).Part of the tissue samples were used to make pathological section,others were made into homogenate.The blood and tissue homogenate were taken for metabolomic analysis based on GC-MS.The original data was analyzed by R software.The original sheet was analyzed by SIMCA-P and other software to find the differential metabolites,and analyzing the trend of these metabolites in the blood.Result:Ascites and cholangiocele were found in the ACLF model.Biochemical parameters suggested that liver injury occurred in both BDL and ACLF groups.Pathological staining confirmed the necrosis of liver cells.Multivariate statistical analysis showed that all the groups were well differentiated.The metabolites with obvious changes were amino acids,some sugars and fatty acids.The metabolic pathways involved are the biosynthesis and metabolism of BCAA?AAA and sulfur-containing amino acids,the metabolism of sugars such as starch,sucrose and galactose and the biosynthesis and metabolism of glycerides,steroids and some phospholipids.Dynamic monitoring of the content changes of these differentiated metabolites showed that 6 of them were positively correlated with the degree of liver injury,including phosphoric acid,tyrosine,tryptophan,urea,glycerin and phosphoylethanolamine,which could be used as possible indicators for clinical evaluation of liver injury.Conclusion:It was found that that dynamic change of some metabolic metabolites was of clinical significance.and they were enriched through metabolite sets enrichment analysis,mostly concentrated in carbohydrate and amino acid metabolism,which can be used for basic physiopathology research and clinical disease treatment.