A pharmacometabonomic approach using predose serum metabolite profiles reveals differences in lipid metabolism in survival and non-survival rats treated with lipopolysaccharide
A pharmacometabonomic approach using predose serum metabolite profiles reveals differences in lipid metabolism in survival and non-survival rats treated with lipopolysaccharide
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使用给药前血清代谢谱的药物代谢组学方法揭示了用脂多糖治疗的存活和非存活大鼠的脂质代谢差异
DOI：
10.1007/s11306-015-0892-6
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发表时间：
2016-01-01
期刊：
影响因子：
3.6
通讯作者：
Zhang, Zunjian
中科院分区：
文献类型：
--
作者：
Dai, Die;Tian, Yuan;Zhang, Zunjian
脂多糖（LPS）与脓毒症和其他致命传染病的临床严重程度相关。越来越多的证据表明，LPS 反应存在显着的遗传变异。然而，仅通过将基因型与临床结果联系起来，几乎无法推断出致病机制。采用集成的液相色谱-质谱和气相色谱-质谱代谢组学分析来了解动物间对 LPS 毒性反应的变异性。对存活和死亡大鼠给药前血清代谢谱的药物代谢组学分析表明，受试者间差异主要与脂质代谢有关。基于最小绝对收缩和选择算子逻辑回归和接受者算子特征分析，选择鞘氨醇、二氢鞘氨醇、棕榈酸、油酸和胆固醇作为LPS毒性预测的最佳子集。因此，使用治疗前代谢物谱的药物代谢组学方法可以为个体水平上预防 LPS 诱发的疾病提供一些启发性指导。
Lipopolysaccharide (LPS) is associated with the clinical severity of sepsis and other fatal infectious diseases. Increasing evidence suggests that there is significant genetic variability in LPS responses. However, little can be inferred on the disease-causing mechanisms only by associating genotypes with clinical outcomes. An integrated liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry metabonomics analysis was employed to understand inter-animal variability in toxic response to LPS. The pharmacometabonomic analysis of predose serum metabolic profiles of the survival and non-survival rats indicates that the inter-subject difference is mainly associated with lipid metabolism. Based on least absolute shrinkage and selection operator logistic regression and receiver operator characteristic analysis, sphingosine, sphinganine, palmitic acid, oleic acid and cholesterol were selected as the best subset for LPS toxicity prediction. Thus, the pharmacometabonomic approach using pretreatment metabolite profiles may provide some heuristic guidance for the prevention of LPS-induced diseases on an individual level.