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在葡聚糖硫酸钠诱导的小鼠结肠炎的不同疾病阶段中产生脂质介质。

Production of lipid mediators across different disease stages of dextran sodium sulfate-induced colitis in mice.

机构信息

Department of Animal Radiology and Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.

Department of Animal Radiology and Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.

出版信息

J Lipid Res. 2018 Apr;59(4):586-595. doi: 10.1194/jlr.M079095. Epub 2018 Feb 2.

DOI:10.1194/jlr.M079095
PMID:29414763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5880491/
Abstract

Although several studies have revealed the role of different lipid mediators in colitis, the comprehensive analysis of their production across different phases of colitis remained unclear. Here, we performed the following analysis in the dextran sodium sulfate (DSS)-induced colitis model using LC-MS/MS. Oral administration of 2% DSS in mice for 4 days resulted in severe intestinal inflammation by day 7, which gradually subsided by day 18. Based on the disease scoring index (assigned on the basis of fecal condition and weight loss), we defined the phases of colitis as induction (days 0-4), acute inflammation (days 4-7), recovery (days 7-9), and late recovery (days 9-18). Across all phases, 58 lipid mediators were detected in the inflamed colon tissue. In the induction phase, the production of n-6 fatty acid-derived prostaglandin E and thromboxane B increased by ∼2-fold. In the acute inflammation phase, the production of n-6 fatty acid-derived leukotrienes increased by >10-fold, while that of n-3 fatty acid-derived hydroxyeicosapentaenoic acids and dihydroxyeicosatetraenoic acids decreased. In the recovery phase, a precursor of protectin D1 (17-hydroxydocosahexaenoic acid) increased over 3-fold. These observations suggested dynamic changes in the production of lipid mediators across different phases of the disease and their potential regulation in healing colitis.

摘要

虽然有几项研究揭示了不同脂质介质在结肠炎中的作用,但它们在结肠炎不同阶段的产生的综合分析仍不清楚。在这里,我们使用 LC-MS/MS 在葡聚糖硫酸钠(DSS)诱导的结肠炎模型中进行了以下分析。在小鼠中口服 2%的 DSS 4 天,在第 7 天导致严重的肠道炎症,第 18 天逐渐缓解。根据疾病评分指数(基于粪便状况和体重减轻来分配),我们将结肠炎的阶段定义为诱导期(第 0-4 天)、急性炎症期(第 4-7 天)、恢复期(第 7-9 天)和晚期恢复期(第 9-18 天)。在所有阶段,在发炎的结肠组织中检测到 58 种脂质介质。在诱导期,n-6 脂肪酸衍生的前列腺素 E 和血栓素 B 的产生增加了约 2 倍。在急性炎症期,n-6 脂肪酸衍生的白三烯的产生增加了 10 倍以上,而 n-3 脂肪酸衍生的羟二十碳五烯酸和二羟二十碳四烯酸的产生减少了。在恢复期,保护素 D1(17-羟基二十二碳六烯酸)的前体增加了 3 倍以上。这些观察结果表明,脂质介质的产生在疾病的不同阶段发生动态变化,它们在治疗结肠炎方面有潜在的调节作用。