Rachmilewitz D, Karmeli F, Okon E
Department of Medicine, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gastroenterology. 1995 Jul;109(1):98-106. doi: 10.1016/0016-5085(95)90273-2.
BACKGROUND & AIMS: Sulfhydryl compounds are essential in maintaining mucosal integrity, and nitric oxide may contribute to tissue injury. The aim of this study was to characterize experimental colitis induced by a sulfhydryl blocker.
Colitis was induced in rats by intracolonic administration of 0.1 mL 3% iodoacetamide with and without addition of 0.1 mg/mL NG-nitro-L-arginine methyl ester (L-NAME) to the drinking water. After death, the distal colonic segment was resected and weighed, and mucosal inflammatory mediator, myeloperoxidase, and NO synthase activities were determined.
Iodoacetamide induced multifocal mucosal erosions and ulceration that were present for up to 1 week. At 3 weeks, the mucosa was almost intact. Colonic wet weight was maximal at 7 days. Myeloperoxidase activity and NO generation were increased in the first 72 hours, and NO synthase activity and prostaglandin E2 generation were increased up to 21 days. Leukotriene B4 and leukotriene C4 generation were increased up to 14 days. One week after iodoacetamide plus L-NAME treatment, lesion area was reduced by 85% and NO synthase activity by 52%.
Inflammatory mediators have an important contribution to the pathogenesis of colonic injury induced by a sulfhydryl alkylator. The protective effect of L-NAME indicates that NO contributes to tissue injury and that its modulation may be a novel approach to treat inflammatory bowel disease.
巯基化合物对于维持黏膜完整性至关重要，而一氧化氮可能导致组织损伤。本研究旨在描述由巯基阻断剂诱导的实验性结肠炎。
通过向大鼠结肠内注射0.1 mL 3%碘乙酰胺诱导结肠炎，同时在饮水中添加或不添加0.1 mg/mL NG-硝基-L-精氨酸甲酯（L-NAME）。处死大鼠后，切除远端结肠段并称重，测定黏膜炎症介质、髓过氧化物酶和一氧化氮合酶活性。
碘乙酰胺诱导多灶性黏膜糜烂和溃疡，可持续长达1周。3周时，黏膜几乎完好无损。结肠湿重在第7天达到最大值。髓过氧化物酶活性和一氧化氮生成在前72小时增加，一氧化氮合酶活性和前列腺素E2生成增加至21天。白三烯B4和白三烯C4生成增加至14天。碘乙酰胺加L-NAME治疗1周后，病变面积减少85%，一氧化氮合酶活性降低52%。
炎症介质对巯基烷化剂诱导的结肠损伤发病机制有重要作用。L-NAME的保护作用表明一氧化氮导致组织损伤，对其进行调节可能是治疗炎症性肠病的新方法。
