Miampamba M, Sharkey K A
Neuroscience and Gastrointestinal Research Groups, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Neurogastroenterol Motil. 1999 Jun;11(3):193-206. doi: 10.1046/j.1365-2982.1999.00150.x.
Nitric oxide (NO) has been implicated in the pathogenesis of inflammatory bowel disease since increased NO production is observed in this disease. NO can react with superoxide to generate peroxynitrite which causes and/or exacerbates colitis. Peroxynitrite, in turn, nitrates tyrosine residues to form nitrotyrosine which can be identified immunohistochemically. We investigated the distribution of neuronal and inducible nitric oxide synthase (iNOS) and nitrotyrosine over time in experimental colitis. Colitis was induced by intracolonic administration of trinitrobenzene sulphonic acid (TNBS) in rats. Animals were killed 1, 2, 7 and 14 days after treatment. Myeloperoxidase activity was used as an index of inflammation, and tissues were examined using immunohistochemistry. Neuronal NOS immunoreactivity was present throughout the colon, and was only slightly reduced 1 day after the induction of colitis. Conversely, iNOS immunoreactivity almost absent in controls dramatically increased in the mucosa and submucosa at the early stages of inflammation. iNOS was present in monocytes and macrophages and also another unidentified cell type. Seven and 14 days after the induction of colitis, iNOS was also found in nerves in the circular muscle and in the myenteric plexus. Nitrotyrosine immunoreactivity present in a few cells in the normal mucosa also increased 1 day after the induction of colitis and decreased thereafter. The pattern of distribution of nitrotyrosine immunoreactivity was distinct from that of iNOS. The increase of iNOS expression at the early stage of inflammation may play a role in causing tissue injury via peroxynitrite formation. The expression of iNOS seen in the enteric nerves in the later stage of inflammation correlates temporally with the beginning of tissue repair and with the re-innervation and compensatory growth of nerves. NO may potentially play a physiological as well as pathological role in experimental colitis.
自从在炎症性肠病中观察到一氧化氮（NO）生成增加以来，NO就被认为与该疾病的发病机制有关。NO可与超氧化物反应生成过氧亚硝酸盐，后者会引发和/或加剧结肠炎。反过来，过氧亚硝酸盐会使酪氨酸残基硝化形成硝基酪氨酸，可通过免疫组织化学方法识别。我们研究了实验性结肠炎中神经元型和诱导型一氧化氮合酶（iNOS）以及硝基酪氨酸随时间的分布情况。通过向大鼠结肠内注射三硝基苯磺酸（TNBS）诱导结肠炎。在治疗后1、2、7和14天处死动物。髓过氧化物酶活性用作炎症指标，并使用免疫组织化学检查组织。神经元型NOS免疫反应性在整个结肠中均有存在，在结肠炎诱导后1天仅略有降低。相反，对照组中几乎不存在的iNOS免疫反应性在炎症早期的黏膜和黏膜下层显著增加。iNOS存在于单核细胞和巨噬细胞以及另一种未鉴定的细胞类型中。在结肠炎诱导后7天和14天，在环行肌和肌间神经丛的神经中也发现了iNOS。正常黏膜中少数细胞中存在的硝基酪氨酸免疫反应性在结肠炎诱导后1天也增加，此后降低。硝基酪氨酸免疫反应性的分布模式与iNOS不同。炎症早期iNOS表达的增加可能通过过氧亚硝酸盐的形成在导致组织损伤中起作用。在炎症后期在肠神经中看到的iNOS表达在时间上与组织修复的开始以及神经的重新支配和代偿性生长相关。NO在实验性结肠炎中可能潜在地发挥生理和病理作用。
