Department of Emergency Medicine, Clinical Research Center for Emergency and Critical Care in Hunan Province, Hunan Provincial Institute of Emergency Medicine, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.
Hunan Provincial Key Laboratory of Molecular Epidemiology, Hunan Normal University, Changsha, Hunan, China.
Eur J Mass Spectrom (Chichester). 2023 Jun;29(3):159-169. doi: 10.1177/14690667231179565. Epub 2023 Jun 20.
The objective of this study is to gain insights into the underlying metabolic transformations that occurred during the whole progression of cecal ligation and puncture (CLP)-induced sepsis, thus providing new targets for its treatment. High-performance liquid chromatography of quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with multivariate statistical techniques was used to detect the s in serum from septic mice. Fifty male mice were divided into two groups, including the sham group ( = 7) and the CLP-induced sepsis group ( = 43). Animals were sacrificed at 1, 3, 5, and 7 days post-CLP and then serum were collected for metabolomic analysis. Multivariate regression analysis was carried out through MetaboAnalyst 5.0, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), to identify the s and screen out the related differential metabolites. Besides, the KEGG pathway analysis was used to analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change (FC > 2.0 or <0.5), variable important in projection (VIP > 1.2), and value ( < 0.05), we found 26, 17, 21, and 17 metabolites in septic mice at 1, 3, 5, and 7 days post-CLP, respectively, compared with that of the sham group. The PCA and PLS-DA pattern recognition showed a cluster-type distribution between the sham group and the CLP group. Dysregulated amino acid metabolism, as well as disturbed nucleotide metabolism, is observed. Several important metabolic pathways were identified between the sham group and the CLP group. Among them, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis showed striking at day 1 post-CLP. At day 3, phenylalanine, tyrosine, and tryptophan biosynthesis changed significantly. However, as the disease process, only pyrimidine metabolism showed the most significant alternation, compared to the sham group. Several differential metabolites were identified in the CLP group compared with that of the sham group and they were presented with dynamic alternation at different time points post-CLP, indicating metabolic disturbance occurred throughout the whole sepsis progression.
本研究旨在深入了解盲肠结扎穿刺（CLP）诱导脓毒症整个进展过程中发生的潜在代谢变化，从而为其治疗提供新的靶点。采用高效液相色谱-四极杆飞行时间质谱联用（HPLC-Q-TOF-MS/MS）结合多变量统计技术检测脓毒症小鼠血清中的代谢物。将 50 只雄性小鼠分为两组，包括假手术组（n=7）和 CLP 诱导的脓毒症组（n=43）。CLP 后 1、3、5 和 7 天处死动物，收集血清进行代谢组学分析。通过 MetaboAnalyst 5.0 进行多变量回归分析，包括主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），以鉴定代谢物并筛选出相关差异代谢物。此外，还使用 KEGG 通路分析分析了所鉴定的代谢物涉及的相关代谢途径。基于 fold change（FC＞2.0 或＜0.5）、variable important in projection（VIP＞1.2）和 P 值（＜0.05），我们在 CLP 后 1、3、5 和 7 天的脓毒症小鼠中分别发现了 26、17、21 和 17 种代谢物，与假手术组相比。PCA 和 PLS-DA 模式识别显示假手术组和 CLP 组之间存在聚类分布。观察到氨基酸代谢和核苷酸代谢紊乱。在假手术组和 CLP 组之间确定了几个重要的代谢途径。其中，苯丙氨酸代谢、苯丙氨酸、酪氨酸和色氨酸生物合成在 CLP 后第 1 天显著增加。第 3 天，苯丙氨酸、酪氨酸和色氨酸生物合成显著改变。然而，随着疾病过程的发展，与假手术组相比，只有嘧啶代谢显示出最显著的改变。与假手术组相比，CLP 组中鉴定出几种差异代谢物，它们在 CLP 后不同时间点呈现动态变化，表明代谢紊乱发生在整个脓毒症进展过程中。
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