使用大鼠结肠炎模型评估炎症性肠病新治疗方法的抗氧化潜力。
Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.
作者信息
Millar A D, Rampton D S, Chander C L, Claxson A W, Blades S, Coumbe A, Panetta J, Morris C J, Blake D R
机构信息
Gastrointestinal Science Unit, London Hospital Medical College.
出版信息
Gut. 1996 Sep;39(3):407-15. doi: 10.1136/gut.39.3.407.
BACKGROUND
Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease.
AIM
To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease.
METHODS
Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease.
RESULTS
The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively.
CONCLUSIONS
The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.
背景
活性氧可能介导炎症性肠病中的组织损伤。氨基水杨酸盐具有抗氧化活性，并且抗氧化剂超氧化物歧化酶和别嘌呤醇在炎症性肠病中已报道有获益。
目的
开发一种便捷技术，用于测试用于炎症性肠病的标准和新型治疗药物的抗氧化潜力。
方法
采用增强化学发光法测量乙酸诱导的结肠炎大鼠结肠活检标本产生的活性氧，并评估传统抗氧化剂、标准疗法及拟用于炎症性肠病的新型疗法的体外效应。
结果
通过证明传统抗氧化剂（叠氮化钠、过氧化氢酶、铜锌超氧化物歧化酶、二甲基亚砜、N-乙酰半胱氨酸和抗坏血酸盐）和标准疗法（5-氨基水杨酸盐和氢化可的松）对乙酸诱导的结肠炎活检标本化学发光的影响模式与先前使用溃疡性结肠炎活检标本报道的相似，验证了该模型。人重组锰超氧化物歧化酶未改变化学发光。两种新型化合物LY231617（10 mM）和安氟替唑（20 mM）分别使化学发光降低了98%（n = 5，p = 0.009）和88%（n = 5，p = 0.03）。
结论
乙酸诱导的结肠炎和溃疡性结肠炎结肠活检标本对一系列传统抗氧化剂和标准治疗的化学发光反应相似，表明该模型是测试炎症性肠病新疗法抗氧化潜力的有用方法。二甲基亚砜、抗坏血酸盐以及新型化合物安氟替唑和LY231617在该模型中的抗氧化作用表明，这些药物在炎症性肠病治疗中值得进一步评估。
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