一氧化氮合酶抑制剂对实验性大鼠结肠炎疗效的研究

背景：炎症性肠病（IBD）中，诱生型一氧化氮合酶（iNOS）合成的高浓度一氧化氮（NO）与肠道炎症和疾病活动度相关。因此抑制iNOS为肠道炎症提供了新的治疗选择。目的：评估NOS抑制剂治疗进展期结肠炎的疗效。方法：予雌性Sprague．Dawlev大鼠含30mg三硝基苯磺酸（TNBS）的50％乙醇溶液0．85ml灌肠，诱导实验性结肠炎。7天后，将大鼠随机分成4组，每组7只，每天分别腹腔注射0．9％NaCl溶液1ml（造模组）、0．2mg／kg地塞米松（DX）、5mg／kg氨基胍（AG）和35mg／kgN-硝基-L-精氨酸甲酯（L-NAME）。另取4只正常大鼠作为正常对照组。通过肠道重量指数、溃疡面积、大体形态和组织学评分以及肠组织髓过氧化物酶（MPO）、丙二醛（MDA）、NOS和iNOS活性、血浆CD62P活性、血清NO含量测定评估疗效。结果：与造模组相比，DX组和AG组肠道重量指数、溃疡面积、大体形态和组织学评分以及肠组织MPO、MDA、NOS和iNOS活性、血浆CD62P活性、血清NO含量均显著降低，L-NAME组肠组织NOS和iNOS活性以及血清NO含量显著降低，但大体形态和组织学评分无改善。结论：选择性iNOS抑制剂AG能通过其抗炎作用减轻进展期肠道炎症，提示AG可作为IBD新的治疗选择，其疗效与DX相似。

Therapeutic Effect of Nitric Oxide Synthase Inhibitor on Experimental Colitis in Rats

Background: High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with gut inflammation and disease activity in inflammatory bowel disease (IBD). Therefore, inhibition of iNOS might serve as a novel experimental approach to treat gut inflammation. Aims: To assess the effect of NOS inhibitor on active colitis. Methods: 30 mg of trinitro-benzene-sulfonic acid (TNBS) dissolved in 0.85 ml of 50% ethanol was administrated intrarectally in Sprague-Dawley female rats to induce experimental colitis. After 7 days, the rats were divided into four groups at random (seven each group). 0.9% saline, dexamethasone (DX) 0.2 mg/kg, aminoguanidine (AG) 5 mg/kg and L-nitro-arginine methylester (L-NAME) 35 mg/kg were administrated intraperitoneally, respectively. Four more healthy rats served as normal controls. The therapeutic effect was evaluated by measuring the ponderal index, the surface area of the ulcers, macroscopical and histological score, activity of myeloperoxidase (MPO), malondialdehyde (MDA), NOS and iNOS in colonic tissue, activity of plasma CD62P and level of serum NO. Results: Compared with the saline group, the ponderal index, the surface area of the ulcers, macroscopical and histological score, activity of MPO, MDA, NOS and iNOS in colonic tissue, activity of plasma CD62P and level of serum NO were lower in the AG and DX groups. Activity of NOS and iNOS, and level of serum NO were lower in the L-NAME group, but macroscopical and histological score was not ameliorated. Conclusions: Selective iNOS inhibitor AG ameliorates TNBS-induced active colitis by its anti-inflammatory effect, it might be a useful new drug to treat IBD, and its therapeutic effect is similar to DX.