Armstrong A M, Campbell G R, Gannon C, Kirk S J, Gardiner K R
Dept. of Surgery, The Queens University of Belfast, Ireland.
Scand J Gastroenterol. 2000 Aug;35(8):832-8. doi: 10.1080/003655200750023200.
Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflammatory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis.
Colitis was induced in Wistar rats. Selective (AMG) and non-selective (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide synthase were given in the drinking water. Colonic citrulline and arginine concentrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system.
Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the agents reduced the severity of colonic inflammation.
Oral administration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colitis.
炎症性肠病（IBD）患者血清和粪便中硝酸盐和亚硝酸盐（一氧化氮的分解产物）浓度升高，提示IBD中一氧化氮合成增加。本研究的目的是评估氨基胍（AMG），一种诱导型一氧化氮合酶的选择性抑制剂，在三硝基苯磺酸（TNBS）诱导的结肠炎中作为一氧化氮抑制剂和炎症调节剂的有效性。
在Wistar大鼠中诱导结肠炎。在饮用水中给予一氧化氮合酶的选择性抑制剂（AMG）和非选择性抑制剂（1-亚硝基-精氨酸甲酯（1-NAME））。使用高效液相色谱法评估结肠中瓜氨酸和精氨酸的浓度。通过宏观评分系统评估结肠炎的严重程度。
1-NAME和AMG均成功降低了一氧化氮的合成。没有证据表明结肠壁中存在底物耗竭。两种药物均未减轻结肠炎症的严重程度。
口服一氧化氮合酶抑制剂可降低结肠壁中一氧化氮的合成。本研究没有提供证据支持一氧化氮在TNBS结肠炎结肠炎症发病机制中的作用。
