A metabonomic characterization of CCl4-induced acute liver failure using partial least square regression based on the GC/MS metabolic profiles of plasma in mice
A metabonomic characterization of CCl4-induced acute liver failure using partial least square regression based on the GC/MS metabolic profiles of plasma in mice
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DOI：
10.1016/j.jchromb.2008.05.049
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发表时间：
2008-07-15
影响因子：
3
通讯作者：
Cheng, Yiyu
中科院分区：
文献类型：
--
作者：
Huang, Xin;Shao, Li;Cheng, Yiyu
研究了不同剂量（100、500和1000 mg/kg）四氯化碳（CCl4）中毒小鼠模型急性肝衰竭（ALF）的代谢紊乱。化学衍生化后，采用气相色谱/质谱（GC/MS）检测小鼠血浆代谢谱。在偏最小二乘回归分析（PLS-RA）的基础上，实现了一种有效的信息提取方法。利用两种y向量对获得的代谢组学数据进行PLS建模，并选择了8种具有不同变化行为的代谢物。CCl4诱导小鼠ALF表现为血浆中谷氨酸、柠檬酸、丝氨酸和苏氨酸升高，α -甘油磷酸、二十二碳六烯酸、棕榈酸和油酸降低。丝氨酸、苏氨酸、棕榈酸和油酸的浓度在对照组和100 mg/kg组之间差异不显著，而在对照组和两个高剂量组之间差异显著。根据所选择的代谢物，讨论了ccl4干扰代谢途径的潜在调控。本研究表明，PLS-RA在探索CCl4中毒的综合代谢效应方面具有很大的潜力，并且能够有效地揭示活性氧（ROS）诱导的ALF的肝毒性机制。(C) 2008 Elsevier B.V.版权所有
This work characterized the metabolism disorders of acute liver failure (ALF) induced by carbon tetrachloride (CCl4) in a mouse model with different dosage of intoxication (100, 500 and 1000 mg/kg). Metabolic profiles of mice plasma were detected by gas chromatography/mass spectrometry (GC/MS) after chemical derivatization. Here an effective information-extracting approach was implemented on the basis of partial least square regression analysis (PLS-RA). PLS modeling was achieved with two kinds of Y-vectors for the acquired metabonomics data and eight metabolites with different changing behaviors were selected. ALF of mice induced by CCl4 was characterized by the elevation of glutamate, citrate, serine and threonine, as well as the decrease of alpha-glycerophosphate, docosahexaenoic acid, palmitic acid and oleic acid in plasma. The difference in the concentrations of serine, threonine, palmitic acid and oleic acid remained insignificant between the control and 100 mg/kg groups, while significant distinction appeared when comparing the control and two higher dosed groups. The underlying regulation of CCl4-perturbed metabolic pathways was discussed according to the selected metabolites. The present study demonstrated a great potential of PLS-RA in exploiting a comprehensive metabolic effects of CCl4 intoxication and its efficient capability to reveal the hepatotoxic mechanism of ALF induced by reactive oxygen species (ROS). (C) 2008 Elsevier B.V. All rights reserved.