Experimental colitis induced by dextran sulphate sodium in mice: beneficial effects of sulphasalazine and olsalazine
Experimental colitis induced by dextran sulphate sodium in mice: beneficial effects of sulphasalazine and olsalazine
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DOI：
10.1046/j.1365-2036.1998.00357.x
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发表时间：
1998-09-01
影响因子：
7.6
通讯作者：
Bylund-Fellenius, AC
中科院分区：
文献类型：
--
作者：
Axelsson, LG;Landstrom, E;Bylund-Fellenius, AC
背景：炎症性肠病的动物模型是人工的，或多或少地代表了人类疾病。然而，近年来，葡聚糖硫酸钠（DSS）诱导的肠道炎症模型已被证明符合一些病理学标准，可以作为一个适当的实验模型。目的：确定这种形式的实验性肠道炎症是否对用于人类炎症性肠病的既定治疗有反应。方法：采用DSS诱导常规Balb/c小鼠和胸腺nu/nu CD-1 （BR）小鼠的肠道炎症反应，并采用文献已证实的5-氨基水杨酸（5-ASA）类抗结肠炎药物磺胺嗪（SASP）和奥萨拉嗪（OLZ）观察其治疗效果。在Balb/c小鼠中测量了反映dss诱导的肠道炎症的参数（体重、结肠长度、脾脏重量、腹泻和直肠出血）。结果：不同治疗方案后，这些指标均有显著改善。研究nu/nu CD-1小鼠的存活率，16天后DSS组的死亡率为50%。SASP （100 mg/kg/day）和OLZ （50 mg/kg/day）显著延长了成活率，分别为29天和38天。SASP和OLZ在10至100 mg/kg/天范围内显示出剂量依赖效应，剂量与人类使用的剂量密切相关。结论：SASP和OLZ可改善dss诱导的肠道炎症，剂量-反应模式提示两种药物的有效治疗部分主要是释放的5-ASA分子。
Background: Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextran sulphate sodium (DSS) induced intestinal inflammation model has recently been shown to fulfil some pathological criteria for an adequate experimental model.Aim: To determine whether this form of experimental intestinal inflammation responds to established therapy used for human inflammatory bowel disease.Methods: DSS was used to induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD-1 (BR) mice, and the well-documented 5-aminosalicylic acid (5-ASA) based anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study therapeutic effects. Parameters which have been shown to reflect DSS-induced intestinal inflammation (body weight, colon length, spleen weight, diarrhoea, and rectal bleeding) were measured in the Balb/c mice.Results: Significant amelioration was seen on these parameters after different treatment protocols. Survival in nu/nu CD-1 mice was studied, and after 16 days a death rate of 50% was noted in the DSS group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolonged the survival to 29 and 38 days, respectively. SASP and OLZ showed a dose-dependent effect in the range between 10 and 100 mg/kg/day, doses closely corresponding to those used in humans.Conclusions: SASP and OLZ are able to ameliorate the DSS-induced intestinal inflammation, The dose-response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5-ASA molecule.