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Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2020-09-23 , DOI: 10.1155/2020/6020247
Zhongquan Xin 1 , Zhenya Zhai 2 , Hongrong Long 1 , Fan Zhang 1 , Xiaojun Ni 3 , Jinping Deng 1 , Lunzhao Yi 4 , Baichuan Deng 1
Affiliation  

Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, ) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process.

中文翻译:

通过 UPLC-Orbitrap-MS/MS 对 DSS 诱导的炎症性肠病 C57BL/6 小鼠肝脏进行代谢分析

肝脏疾病常发生于炎症性肠病 (IBD) 患者;然而,IBD 诱导的肝脏疾病在内在分子水平(主要代谢物)和治疗靶点的变化仍然没有得到很好的表征。首先,建立了 C57BL/6 小鼠 DSS 慢性结肠炎的精细和翻译相关模型,并使用天蚕素 A 和抗生素作为干预措施。我们发现,肿瘤坏死因子水平(TNF) - α,白介素(IL)-1 β和小鼠肝组织中的 IL-6 在 DSS 治疗的背景下高度增加,但被天蚕素 A 和抗生素降低。随后,通过 UPLC-Orbitrap-MS/MS 进行了非靶向代谢组学分析,以揭示代谢特征并试图找到 IBD 中发生的肝脏疾病的潜在治疗靶点。值得注意的是,综合数据库确定了 133 种代谢物。代谢网络和通路分析表明,IBD小鼠肝脏代谢紊乱主要集中在胆汁酸代谢、花生四烯酸代谢、氨基酸代谢和类固醇激素生物合成,而这些紊乱通过天蚕素A和抗生素治疗得到调节或逆转. 此外,排名前 20 的代谢物,如谷胱甘肽、麦芽糖、花生四烯酸和硫胺素,)加上正交偏最小二乘判别分析 (OPLS-DA) 的项目值 (VIP > 1) 的可变重要性,可以通过天蚕素 A 和抗生素处理上调或下调。Spearman 相关性分析表明,大多数生物标志物与细胞因子(TNF- α、IL-、IL-6 和 IL-10)具有显着相关性,表明这些生物标志物可能作为直接或间接相互作用的潜在靶标与天蚕素 A 和抗生素一起影响肝脏炎症。总的来说,我们的结果扩展了对 IBD 中发生的肝脏疾病的分子改变的理解,并为发现 IBD 过程中的潜在治疗靶点提供了机会。
更新日期:2020-09-23
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