Dikopoulos N, Nüssler A K, Liptay S, Bachem M, Reinshagen M, Stiegler M, Schmid R M, Adler G, Weidenbach H
Department of Internal Medicine I, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany.
Eur J Clin Invest. 2001 Mar;31(3):234-9. doi: 10.1046/j.1365-2362.2001.00802.x.
The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel diseases (IBD) is controversially discussed. The aim of the present study was to investigate the role of NO inhibition in the acute phase of rat 2,4,6-trinitrobenzenesulphonic acid (TNB)-colitis. To inhibit NO synthesis we used aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS). TNB-colitis was induced in rats with and without pretreatment with AG (200 mg kg-1 body weight in the drinking water). The severity of colitis was observed over a period of 7 days. On days 1 and 2, AG reduced concentrations of plasma nitrate and nitrite as well as of portal 6-keto-prostaglandin 1alpha. AG pretreatment increased colonic damage and inflammatory response, assessed by colonic myeloperoxidase and serum lactate dehydrogenase activity, macroscopic damage score, tumour necrosis factor-alpha concentration in stool and colonic glutathione content. The AG-treated group showed a higher and prolonged nuclear factor kappaB (NF-kappaB)/Rel binding activity in the colon. We conclude that NOS inhibition by AG is not beneficial in acute intestinal inflammation. With regard to appropriate therapeutic strategies, NF-kappaB/Rel activation might be a more suitable target.
一氧化氮（NO）在炎症性肠病（IBD）病理生理学中的作用存在争议。本研究的目的是探讨NO抑制在大鼠2,4,6-三硝基苯磺酸（TNB）结肠炎急性期的作用。为了抑制NO合成，我们使用氨基胍（AG）作为诱导型一氧化氮合酶（iNOS）的选择性抑制剂。在有或没有AG预处理（饮用水中200 mg/kg体重）的大鼠中诱导TNB结肠炎。观察结肠炎的严重程度达7天。在第1天和第2天，AG降低了血浆硝酸盐和亚硝酸盐以及门静脉6-酮-前列腺素1α的浓度。AG预处理增加了结肠损伤和炎症反应，通过结肠髓过氧化物酶和血清乳酸脱氢酶活性、宏观损伤评分、粪便中肿瘤坏死因子-α浓度和结肠谷胱甘肽含量来评估。AG治疗组在结肠中显示出更高且持续时间更长的核因子κB（NF-κB）/Rel结合活性。我们得出结论，AG抑制NOS对急性肠道炎症无益。关于适当的治疗策略，NF-κB/Rel激活可能是一个更合适的靶点。
