Qiu B, Pothoulakis C, Castagliuolo I, Nikulasson S, LaMont J T
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Am J Physiol. 1999 Feb;276(2):G485-90. doi: 10.1152/ajpgi.1999.276.2.G485.
Reactive oxygen metabolites (ROMs) contribute to the pathophysiology of intestinal inflammation. Our aim was to ascertain the involvement of ROMs in experimental ileitis in rats produced by toxin A of Clostridium difficile. Intraluminal toxin A caused a significant increase in hydroxyl radical and hydrogen peroxide production by ileal microsomes starting 1 h following toxin exposure and peaking at 2-3 h, and this was inhibited by pretreatment with DMSO, a ROM scavenger, or superoxide dismutase (SOD), which inactivates ROMs. In contrast, mucosal xanthine oxidase increased only slightly after toxin A exposure, and allopurinol, an inhibitor of xanthine oxidase, had no effect on toxin A-associated intestinal responses. Induction of neutropenia resulted in reduction of toxin-mediated free radical formation, fluid secretion, and permeability. The enterotoxic effects of C. difficile toxin A were associated with increased ROM release in ileal tissues, and the ROM inhibitors DMSO and SOD inhibited these effects. This suggests that ROMs released during toxin A enteritis are released primarily from neutrophils invading the inflamed bowel segment.
活性氧代谢产物（ROMs）参与肠道炎症的病理生理过程。我们的目的是确定ROMs在艰难梭菌毒素A所致大鼠实验性回肠炎中的作用。肠腔内毒素A在毒素暴露后1小时开始使回肠微粒体产生的羟自由基和过氧化氢显著增加，并在2 - 3小时达到峰值，而用ROM清除剂二甲基亚砜（DMSO）或使ROM失活的超氧化物歧化酶（SOD）预处理可抑制这种增加。相比之下，毒素A暴露后黏膜黄嘌呤氧化酶仅略有增加，黄嘌呤氧化酶抑制剂别嘌呤醇对毒素A相关的肠道反应无影响。诱导中性粒细胞减少导致毒素介导的自由基形成、液体分泌和通透性降低。艰难梭菌毒素A的肠毒素作用与回肠组织中ROM释放增加有关，ROM抑制剂DMSO和SOD可抑制这些作用。这表明毒素A性肠炎期间释放的ROMs主要来自侵入炎症肠段的中性粒细胞。
