Studies On Metabonomics Of Bladder Carcinoma And Liver Injury Induced By Liver Transplantation Based On GC-MS

Metabonomics, which defined as "the quantitative measurement of dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification", has now been widely used in the research of disease diagnosis, pharmacology and toxicology. The main techniques for metabonomics research are NMR, GC-MS and LC-MS. In these technologies, GC-MS, with searchable standard database, which facilitates the identification of metabolites, can simultaneouly determine various kinds of endogenous (amino acids, organic acids, fatty acids and esters, sugar and steroid substances). In addition, it also combines the excellent separation capability of GC and the high sensitivity of MS, thus it is considered as an ideal tool for the metabonomics study.In this thesis, GC-MS methods were established for characterizing the metabolite profiles of the urine and serum, and the methods were used in the metabonomics studies of bladder carcinoma and liver injury induced by liver transplanted. The main content of this study is presented as follows:(1) A stable and reliable GC-MS analytical method was established to obtain the metabolite profiles of human urine. NIST 2002 was used for the identification of the detected metabolites. The procedures of sample preparation, derivatizatiion conditions and chromatographic conditions were optimized. The method was validated and applied successfully in the comparison of urine metabolite profiles from patients of bladder carcinoma and the health. It was found that four endogenous metabolites were significantly different in two groups, which may be used as potential biomarkers of bladder carcinoma.(2) A GC-MS method was applied to the metabonomics study of liver injury of rat induced by liver transplantation. Principal components analysis (PCA) was used for recognizing the different metabolic patterns between the transplantation and control groups. The time-dependent metabolic changes were discovered from the PCA score plots of the metabonomics data. Compared with the results of liver histological and serum biochemical examinations, the changes not only can provide the evidence of damage of liver, but also reflect the information about other organ, which can not be obtained by conventional test.