Systemic Responses of Mice to Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis Using 1H NMR Spectroscopy
Systemic Responses of Mice to Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis Using 1H NMR Spectroscopy
复制标题
使用 1H NMR 波谱法观察小鼠对硫酸葡聚糖钠诱导的急性溃疡性结肠炎的全身反应
DOI：
10.1021/pr4002383
复制
发表时间：
2013-06-01
影响因子：
4.4
通讯作者：
Wang, Yulan
中科院分区：
文献类型：
--
作者：
Dong, Fangcong;Zhang, Lulu;Wang, Yulan
基因突变和环境因素之间的相互作用被认为是炎症性肠病（IBD）的病因。虽然上述研究得到了重点关注，但与IBD相关的时间特异性和器官特异性代谢变化仍然缺乏。在这里，我们通过提供含有3%葡聚糖硫酸钠（DSS）的水诱导小鼠急性溃疡性结肠炎7天，并采用基于H-1核磁共振（NMR）的代谢组学方法研究血浆、尿液和一系列生物组织的代谢变化，并补充血清临床化学和组织病理学信息。我们发现，dss诱导的急性溃疡性结肠炎导致血浆中氨基酸水平显著升高，结肠中膜相关代谢物和一系列核苷酸、核碱基和核苷水平降低。此外，观察到急性结肠炎引起的肝脏核苷酸水平升高，并伴有葡萄糖水平降低。dss诱导的急性结肠炎也导致脾脏中氧化谷胱甘肽水平升高和牛磺酸水平降低。此外，急性结肠炎导致尿液中肠道微生物共代谢物水平下降，同时柠檬酸循环中间体增加。这些发现表明，dss诱导的急性结肠炎会引起脂质和能量代谢紊乱，结肠和肝脏受损，抗氧化和抗炎反应增强，肠道微生物群落紊乱。这里获得的信息提供了dss诱导的急性溃疡性结肠炎发展过程中时间依赖性和整体代谢变化的细节，这可能有助于发现IBD管理的新治疗靶点。
The interplay between genetic mutation and environmental factors is believed to contribute to the etiology of inflammatory bowel disease (IBD). While focused attention has been paid to the aforementioned research, time-specific and organ-specific metabolic changes associated with IBD are still lacking. Here, we induced acute ulcerative colitis in mice by providing water containing 3% dextran sulfate sodium (DSS) for 7 days and investigated the metabolic changes of plasma, urine, and a range of biological tissues by employing a H-1 nuclear magnetic resonance (NMR)-based metabonomics approach with complementary information on serum clinical chemistry and histopathology. We found that DSS-induced acute ulcerative colitis leads to significant elevations in the levels of amino acids in plasma and decreased levels in the membrane-related metabolites and a range of nucleotides, nucleobases, and nucleosides in the colon. In addition, acute-colitis-induced elevations in the levels of nucleotides in the liver were observed, accompanied by reduced levels of glucose. DSS-induced acute colitis also resulted in increased levels of oxidized glutathione and attenuated levels of taurine in the spleen. Furthermore, acute colitis resulted in depletion in the levels of gut microbial cometabolites in urine along with an increase in citric acid cycle intermediates. These findings suggest that DSS-induced acute colitis causes a disturbance of lipid and energy metabolism, damage to the colon and liver, a promoted antioxidative and anti-inflammatory response, and perturbed gut microbiotal communities. The information obtained here provided details of the time-dependent and holistic metabolic changes in the development of the DSS-induced acute ulcerative colitis, which could be useful in discovery of novel therapeutic targets for management of IBD.