Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Dig Dis Sci. 2010 Oct;55(10):2797-804. doi: 10.1007/s10620-009-1112-x. Epub 2010 Jan 22.
Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated 2,4,6-trinitrobenzine sulfonic acid (TNBS)-induced colitis in mice.
The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day when TNBS was administered and throughout the remaining study period. The distal colon was removed, and ulcerative lesions were subsequently evaluated with macroscopic damage scores. Furthermore, thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity in colonic mucosa were measured as indices of lipid peroxidation and neutrophil infiltration. The expressions of TNF-α in colonic mucosa were also measured by enzyme-linked immunosorbent assay. In additional experiments in vitro, CD4(+) T cells isolated from the spleen were stimulated with anti-CD3/CD28 Ab, and the cells and supernatants were collected and evaluated for TNF-α expression.
The increased colonic damage after TNBS administration was significantly inhibited by the treatment with CO. Furthermore, CO significantly inhibited the increases in TBA-reactive substances, MPO activity and TNF-α production in colonic mucosa after the induction of TNBS colitis. In CD4(+) T cells isolated from mice treated with CO inhalation, the production of TNF-α was significantly inhibited.
The inhalation of CO protected mice from developing intestinal inflammation. Based on these data, the beneficial effects of CO in a murine colitis model may be attributed to its anti-inflammatory properties.
一氧化碳（CO）长期以来被认为是一种有毒气体，但最近的研究表明，它在各种动物模型中具有抗炎作用。本研究旨在探讨吸入 CO 是否能改善 2,4,6-三硝基苯磺酸（TNBS）诱导的小鼠结肠炎。
CO 处理组在 TNBS 给药当天开始在封闭笼中以 200 ppm 的 CO 浓度暴露，直至研究结束。切除远端结肠，随后用宏观损伤评分评估溃疡性病变。此外，还测量了结肠黏膜中硫代巴比妥酸（TBA）反应性物质和组织相关髓过氧化物酶（MPO）活性，作为脂质过氧化和中性粒细胞浸润的指标。通过酶联免疫吸附试验测量结肠黏膜中 TNF-α 的表达。在体外的附加实验中，用抗 CD3/CD28 Ab 刺激从脾中分离的 CD4(+) T 细胞，并收集细胞和上清液，评估 TNF-α 的表达。
TNBS 给药后结肠损伤的增加被 CO 处理显著抑制。此外，CO 显著抑制了 TNBS 结肠炎诱导后结肠黏膜中 TBA 反应性物质、MPO 活性和 TNF-α 产生的增加。在吸入 CO 处理的小鼠中分离的 CD4(+) T 细胞中，TNF-α 的产生显著受到抑制。
CO 的吸入保护小鼠免受肠道炎症的发生。基于这些数据，CO 在小鼠结肠炎模型中的有益作用可能归因于其抗炎特性。
