Metabolic profiling analysis of a D-galactosamine/lipopolysaccharide-induced mouse model of fulminant hepatic failure
Metabolic profiling analysis of a D-galactosamine/lipopolysaccharide-induced mouse model of fulminant hepatic failure
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DOI：
10.1021/pr0606326
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Wei, Lai
中科院分区：
文献类型：
--
作者：
Feng, Bo;Wu, Shengming;Wei, Lai
本研究的目的是表征代谢中间产物的变化，并研究由D-半乳糖胺/脂多糖（GaIN/LPS）诱导的暴发性肝衰竭（FHF）小鼠模型的代谢特征。使用气相色谱/飞行时间质谱法检测血浆代谢物水平，并将获得的数据转移到Simca-P中，并使用主成分分析（PCA）进行处理。从研究中发现的267种不同化合物中总共鉴定出45种代谢物。尽管对照组和FHF组的血浆水平存在显著差异，但在GaIN/LPS处理后，未观察到异生或糖酵解的差异。我们的数据还表明，酮体的产生，以及三羧酸和尿素循环，受到抑制。PCA数据表明，5-羟基吲哚乙酸，葡萄糖，β-羟基丁酸和磷酸盐参数在每个主成分上的权重最高，并且它们是有助于组分离的最重要的代谢物。总之，这种代谢组学方法可以作为一个强大的工具来表征代谢中间体的变化，并在某些病理生理条件下，如FHF的代谢标志物的搜索。我们的数据还表明，血浆中5-羟基吲哚乙酸、葡萄糖、β-羟基丁酸和磷酸盐浓度的组合是FHF的潜在标志物，以及FHF的早期预后。
The purpose of this study was to characterize the changes in metabolic intermediates and to investigate the metabolic profile of a mouse model of fulminant hepatic failure (FHF), induced by D-galactosamine/ lipopolysaccharide (GaIN/LPS). Plasma metabolite levels were detected using gas chromatography/ time-of-flight mass spectrometry, and the acquired data were transferred into Simca-P and processed using principal components analysis ( PCA). In total, 45 metabolites were identified from the 267 distinct compounds found in the study. Whereas significant differences were noted in the plasma levels of the control and FHF groups, no differences in gluconeogenesis or glycolysis were noted following GaIN/LPS treatment. Our data also suggest that the production of ketone bodies, and the tricarboxylic acid and urea cycles, was inhibited. PCA data suggest that 5-hydroxyindoleacetic acid, glucose, beta-hydroxybutyrate, and phosphate parameters had the highest weights on each of the principal components, and that they were the most important metabolites contributing to the separation of groups. In conclusion, this metabonomic approach can be used as a powerful tool to characterize changes in metabolic intermediates and to search for metabolic markers under certain pathophysiological conditions, such as FHF. Our data also demonstrate that a combination of 5-hydroxyindoleacetic acid, glucose, beta-hydroxybutyrate, and phosphate concentrations in the plasma is a potential marker for FHF, as well as for the early prognosis of FHF.