Rachmilewitz D, Stamler J S, Karmeli F, Mullins M E, Singel D J, Loscalzo J, Xavier R J, Podolsky D K
Gastrointestinal Unit, Massachusetts General Hospital, Boston.
Gastroenterology. 1993 Dec;105(6):1681-8. doi: 10.1016/0016-5085(93)91063-n.
Excessive production of nitric oxide, characteristic of inflamed states, may have deleterious effects through its facile conversion (in the presence of O2) to peroxynitrite, which promotes lipid and sulfhydryl oxidation. This study assessed the effect of peroxynitrite on the rat colon.
Peroxynitrite was administered intrarectally to rats. One, 3, 7, and 21 days after treatment, a distal colonic segment was isolated and tissue was obtained for histological evaluation and determination of myeloperoxidase activity and NOX, and eicosanoids generation.
Within 24 hours, the exposed segment was edematous and congested with occasional hemorrhagic mucosal ulceration. On day 7, the lumen was narrow; at day 21, there were signs of stenosis. Histological analysis showed transmucosal necrosis, acute inflammation, and exudative edema 24 hours after treatment. Surface re-epithelization and infiltration of granulation tissue were present at 1 week. Resolution of edema, mucin repletion, thickening of muscularis mucosa and propria, and fibrosis were observed at 3 weeks. Significant increase in NOX generation and myeloperoxidase and NO synthase activities were observed at 24 hours, whereas enhanced leukotriene generation was observed only at 21 days.
Peroxynitrite-induced colonic inflammation provides a novel model of NO-related tissue injury and offers the opportunity to further explore the potential role of NO in the pathogenesis of inflammatory bowel disease.
一氧化氮过度产生是炎症状态的特征，它可能通过（在氧气存在下）轻易转化为过氧亚硝酸盐而产生有害影响，过氧亚硝酸盐会促进脂质和巯基氧化。本研究评估了过氧亚硝酸盐对大鼠结肠的影响。
将过氧亚硝酸盐经直肠给予大鼠。在治疗后1天、3天、7天和21天，分离远端结肠段，获取组织用于组织学评估以及髓过氧化物酶活性、NOX和类花生酸生成的测定。
在24小时内，暴露的肠段出现水肿和充血，偶见出血性黏膜溃疡。在第7天，肠腔变窄；在第21天，出现狭窄迹象。组织学分析显示，治疗后24小时出现透黏膜坏死、急性炎症和渗出性水肿。1周时可见表面重新上皮化和肉芽组织浸润。3周时观察到水肿消退、黏液补充、黏膜肌层和固有层增厚以及纤维化。在24小时时观察到NOX生成、髓过氧化物酶和NO合酶活性显著增加，而仅在21天时观察到白三烯生成增强。
过氧亚硝酸盐诱导的结肠炎症提供了一种与NO相关的组织损伤新模型，并为进一步探索NO在炎症性肠病发病机制中的潜在作用提供了机会。
