Gas Chromatography-mass Spectrometry Based Serum Metabolomics Study Of Gout And The Quzhuotongbi Decoction Treatment

Objective To elucidate the pathogenesis of gout and provide a potential aid for the accurate diagnosis or treatment of gout.A gas chromatography-mass spectrometry(GC-MS)based metabolic profiling method was employed to explore the distinctive metabolic patterns in gout patients and the effects of Quzhuotongbi decoction(QZTBD)on urate and other metabolites in the sera of hyperuricemia model rats.Method Serum metabolomics fingerprint was performed by using GC-MS method.Multivariate statistical analysis including the principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)were used to assess the metabolic data.Significant difference between groups was shown in PCA score plot.Variable importance for project values(VIP)and non-parameters tests were combined to pick out the significant metabolic changes.Results Compared with the control group,the serum metabolic signature of patients with gout was featured by increased levels of metabolites related to nucleotide metabolism(hypoxanthine,uric acid and uridine),carbohydrate metabolism(2,3-Dihydroxybutyrate,D-threitol,D-gluconic acid,myo-Inositol,etc.)and amino acid metabolism(3-hydroxy-3-methylbutyrate,L-ornithine and indole-3-lactic acid),decreased levels of lipids(monoethanolamine,glycerol,glyceric acid,etc.),glycine and hypotaurine.After the administration of yeast extract paste,hyperuricemia model was established successfully.The levels of urate,lactate,pyruvate and ornithine were significantly increased,and xanthine,glyconic acids(ribonate,galactonate),amino acids(aspartate,proline,glutamine,serine,pyroglutamate,glutamate)and glucose were down-regulated greatly in the model rats.11 metabolites which contributed to most of classification were selected.8 of them were identified,including urate,pyruvate,lactate,ethanolamine,several amino acids(tyrosine,serine,proline,N-Acetyl-L-Lysine).Conclusions Compared with the control group,the disease-associated metabolic perturbations involved in multiple metabolic pathways including purine metabolism and occurred in gout patients.In hyperuricemia model rats,the nucleotide metabolism,amino acid metabolism and glycolytic pathway were influenced by yeast administration.As compared to the model rats,the serum uric acid levels were lowered markedly under the treatment of allopurinol or QZTBD.The different influences on xanthine,glutamate pyroglutamate and galactonate suggested there were different mechanism of two drugs in urate-lowering therapy.