Purpose: Substantial evidence indicates that lipopolysaccharide (LPS) exposure can lead to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Previous metabolomic studies have mainly focused on LPS-induced depression or hepatic and renal effects. However, no comprehensive metabolomics-based analysis of the serum, liver, kidney, hippocampus, and heart following exposure to LPS has been undertaken to date.
Material and Methods: Male Sprague–Dawley rats were randomly allocated to a control and a LPS-treated group (n=8). LPS for 2 weeks (0.5 mg/kg every other day) was given via intraperitoneal injection. Gas chromatography–mass spectrometry (GC–MS) was used for metabolite determination, while multivariate statistical analysis was performed to identify differentially expressed metabolites between the two groups.
Results: Our study revealed that 24, 13, 12, 7, and 12 metabolites were differentially expressed between the LPS treatment group and the control group in the serum, liver, kidney, hippocampus, and heart, respectively. We further identified that these metabolic changes were mainly involved with aminoacyl-tRNA biosynthesis; glutathione metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; arginine biosynthesis; bile acid biosynthesis; and glycerolipid metabolism.
Conclusion: We have systematically elucidated the metabolic changes underlying LPS-induced SIRS, thereby providing insight into the mechanisms associated with these alterations.

Keywords: systemic inflammatory response syndrome, metabolites, gas chromatography–mass spectrometry, multivariate statistical analysis


中文翻译：

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基于代谢组学综合评价脂多糖诱导的大鼠变化。

目的：大量证据表明，脂多糖 (LPS) 暴露可导致全身炎症反应综合征 (SIRS) 和多器官衰竭。以前的代谢组学研究主要集中在 LPS 诱导的抑郁或肝肾效应。然而，迄今为止，尚未对暴露于 LPS 后的血清、肝脏、肾脏、海马和心脏进行全面的基于代谢组学的分析。
材料与方法：雄性 Sprague-Dawley 大鼠被随机分配到对照组和 LPS 治疗组 (n = 8)。通过腹膜内注射给予 LPS 2 周（每隔一天 0.5 mg/kg）。气相色谱 - 质谱（GC-MS）用于代谢物测定，同时进行多变量统计分析以确定两组之间差异表达的代谢物。
结果：我们的研究表明，LPS 治疗组和对照组之间分别有 24、13、12、7 和 12 种代谢物在血清、肝脏、肾脏、海马和心脏中的差异表达。我们进一步确定这些代谢变化主要与氨酰-tRNA生物合成有关。谷胱甘肽代谢；乙醛酸和二羧酸代谢；甘氨酸、丝氨酸和苏氨酸代谢；精氨酸生物合成；胆汁酸生物合成；和甘油脂代谢。
结论：我们系统地阐明了 LPS 诱导的 SIRS 的代谢变化，从而深入了解与这些变化相关的机制。

关键词：全身炎症反应综合征，代谢物，气相色谱-质谱，多变量统计分析