Study Of Triptolide Induced Hepato-toxicology By MS-based Metabonomics Approaches

Metabonomics is a new system biology technology after genomics, transcriptomics and proteomics. It is defined as "the quantitative measurement of the multiparametric time-related metabolic responses of a complex system to a pathophysiological intervention or genetic modification", and has been widely used in the researches of pharmacology and biological sciences. Metabonomics encompasses comprehensive and simultaneous systematic profiling of metabolites and their systematic temporal changes in response to stimulus of xenobiotics, environment, and genetics in whole organisms. Here we are going to introduce a method which is established by liquid chromatography-mass spectrometry technique combined with the existed gas chromatography-mass spectrometry technique, and applied with the liver tissue and serum, to investigate the metabonome of the triptolide induced liver injure in rats. Different systematic profilings of metabolites were observed, and examined by PLS-DA method, discriminated by VIP and ANOVA method. The mechanism of the response to stimulus of triptolide with different dose and the toxical mechanism of triptolide were tried to be found. The possible fusion method for data from mutil-analytical plateform was discussed.Firstly, a metabonomic study of the triptolide induced liver injure in rats was described. Liquid chromatography-mass spectrometry (LC-MS) technique was employed to analyze the rat metabonome in serum. Partial least square-discriminant analysis (PLS-DA) was used to analyze the metabonome difference between the control, low, middle and high dose triptolide treated groups. Different metabolites were founded in rat serum metabonome, respectively, via both the parameters of variable importance in the projection (VIP) and ANOVA. The hepatotoxicity effect of triptolide was investigated through the selected responsor metabolites. The cholic metabolism and lecithoid metabolism were seriously disturbed by triptolide treatment.Secondly, a metabonomic study of the triptolide induced liver injure in rats was described. Gas chromatography-mass spectrometry (GC-MS) technique was used to analyze the rat metabonome in serum. PLS-DA was used to analyze the metabonome difference between the control, low, middle and high dose triptolide treated samples. The twelve metabolites in serum and ten metabolites in liver tissue were selected in rat serum metabonome, respectively, via both the parameters of VIP and ANOVA. The energy metabolism and lipids metabolism were seriously disturbed by triptolide treatment.Thirdly, Multi-block principal components analysis was applied for the data sets of LC-MS and GC-MS based liver metabonomics. This data analytical method extracted the "common dose-toxical trend of triptolide" in above two sets and improved the efficency of classification.