5-Aminosalicylic Acid Inhibits Colitis-Associated Colorectal Dysplasias in the Mouse Model of Azoxymethane/Dextran Sulfate Sodium-Induced Colitis
5-Aminosalicylic Acid Inhibits Colitis-Associated Colorectal Dysplasias in the Mouse Model of Azoxymethane/Dextran Sulfate Sodium-Induced Colitis
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DOI：
10.1002/ibd.20489
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发表时间：
2008-10-01
影响因子：
4.9
通讯作者：
Cooper, Harry S.
中科院分区：
文献类型：
--
作者：
Clapper, Margie L.;Gary, Monique A.;Cooper, Harry S.
背景资料：抗结肠炎药物5-氨基水杨酸（5-阿萨）对结肠炎相关结直肠癌风险的影响仍存在争议。在氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠炎相关瘤形成的Swiss韦伯斯特模型中评价5-阿萨的化学预防活性。并在研究的剩余时间内随机接受溶媒或5-阿萨（75、150和225 mg/kg）。DSS治疗从9周龄开始，持续3个周期。在处死时结果：在所有给药组中，剂量与结肠发育不良的发生率呈负相关（P = 0.03），接受75 mg/kg 5-阿萨的动物表现出的发育不良数量是AOM/DSS对照组的56%（平均值+/- SEM：7.6 ± 1.4和13.6 ± 2.7。分别）。给予75 mg/kg 5-阿萨降低了扁平发育不良的平均多样性，（药物治疗组为1.8 +/- 0.4，AOM/DSS对照组为5.6 +/- 1.2）和息肉样发育不良的负担（肿瘤负荷：药物治疗组为6.7 +/- 2.7单位，AOM/DSS对照组为14.9 +/- 3.9单位）显著（P = 0.002和0.04）。分别）。75 mg/kg组的炎症最轻。结论：这些数据表明，低剂量5-阿萨可能是有效的，在预防结肠炎相关的发育不良，并提供了强有力的支持，优化这种治疗方法，以预防结肠肿瘤的溃疡性结肠炎患者。（炎症性肠病2008; 14：1341-1347）
Background: The impact of the antiinflammatory agent 5-aminosalicylic acid (5-ASA) on the risk for colitis-associated colorectal cancer remains controversial. The chemopreventive activity of 5-ASA was evaluated in the Swiss Webster model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated neoplasia.Methods: Mice were injected with AOM (7.4 mg/kg i.p.) and randomized to receive either vehicle or 5-ASA (75, 150, and 225 mg/kg) for the remainder of the study. DSS treatment began at 9 weeks of age and continued for 3 cycles. At the time of sacrifice (18 weeks of age), the entire colon and rectum were processed for histopathologic examination.Results: An inverse trend was observed between dose and Multiplicity of colonic dysplasias in all drug-treated groups (P = 0.03), with animals receiving 75 mg/kg 5-ASA exhibiting 56% of the number of dysplasias of the AOM/DSS controls (mean +/- SEM: 7.6 +/- 1.4 and 13.6 +/- 2.7. respectively). Administration of 75 mg/kg 5-ASA decreased both the mean multiplicity of flat dysplasias (1.8 +/- 0.4 for drug-treated versus 5.6 +/- 1.2 for AOM/DSS control) and the burden of polypoid dysplasias (tumor burden: 6.7 +/- 2.7 for drug-treated versus 14.9 +/- 3.9 units for AOM/DSS controls) significantly (P = 0.002 and 0.04. respectively). Inflammation was least severe in the 75 mg/kg group. which exhibited the fewest number of colorectal tumors.Conclusions: These data suggest that low-dose 5-ASA may be efficacious in preventing colitis-associated dysplasias and provide strong support for optimizing this therapy for the prevention of colonic neoplasms in patients with ulcerative colitis. (Inflamm Bowel Dis 2008; 14:1341-1347)