选择性环氧合酶-2抑制剂对大鼠溃疡性结肠炎作用实验研究.docVIP

选择性环氧合酶-2抑制剂对大鼠溃疡性结肠炎作用实验研究 　　【摘要】 目的 明确选择性环氧合酶COX-2抑制剂塞来昔布对2、4、6三硝基苯磺酸（TNBS）诱导的大鼠溃疡性结肠炎的作用，并初步探讨其作用机制。方法 将大鼠分为三组，第1组和第2组为造模组，用0.25 ml TNBS乙醇溶液（TNBS浓度25 mg/ml，乙醇浓度50％），灌肠，诱导大鼠实验性溃疡性结肠炎模型。造模组大鼠于造模前3 h开始，分别给予塞来昔布（12．5 mg/kg）和蒸馏水(1 ml/0．3 mg)，2次/d，共7 d。第3组为正常对照组。第7 d实验结束时处死所用存活动物，观察结肠黏膜损伤程度，并用ELISA法检测IL-1β、IL-10、TNF-β的浓度。结果 造模组结肠损伤积分为（8．20±1．96）（第1组）和（12．05±2．30）（第2组）均显著高于正常对照组（0．64±0．15）（P值均 　　【关键词】 溃疡性结肠炎；选择性环氧合酶-2抑制剂；炎症介质 　　 　　Study of celecoxib on rat ulcerative colitis induced by trinitrobenzene sulfonic acid JIN lei, CAO qin,CHEN Xi-mei.Department of gastroenterology,the Central Hospital of Putuo district,Shanghai,200062，China 　　【Abstract】 Objective An investigation was conducted to assess the effects and mechanism of celecoxib ［a selective cyclooxygenase(COX)-2 inhibitor］ on a rat ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS). Methods The rats were divided into three groups .Group 1 and Group 2 were experimental groups. Ulcerative colitis was conducted by TNBS (25 mg/ml) in a vehicle of 50% ethanol (0．25 ml) in rats. Three hours before induction of ulcerative colitis.the rats were beginning and continuing to treat orally with celecoxib（12．5 mg/kg）and distilled water (1 ml/0．3 mg) twice per day for 7 days. Group 3 was healthy control group.All rats that survived at the end of the experiment (7 d) were killed and the severity of damage were assessed. The IL-1β、IL-10、TNF-βconcentrations were tested by ELISA. Results The colonic damage scores were8．20±1．96 in group 1 and (12．05±2．30)in group 2. Both were significantly higher than that of group 3 (0．64±0．15) (P[１]，因此用选择性COX-2抑制剂预防IBD患者中结直肠癌的发生是非常有益的[2,3]。我们采用半抗原三硝基苯磺酸（TNBS）灌肠建立大鼠细胞免疫反应性炎症性肠病模型，研究选择性COX-2抑制剂对实验性溃疡性结肠炎（UC）炎症的作用，并探讨其与相关白介素和肿瘤坏死因子的关系。 　　 　　1 材料与方法 　　 　　1．1 动物 雄性SD大鼠，体质量240~370 g（购自上海试验动物研究所），在恒温、恒湿条件下喂养，每日光照12 h，饲料、水均不受限制。 　　1．2 药品和试剂 塞来昔布（celecoxib，商品名：西乐葆）购自西尔公司。5％TNBS水溶液购自Sigma公司，ELISA试剂盒购自南京生物科技有限公司。 　　1．3 动物模型的建立 利用细胞免疫法，即以乙醇为肠黏膜 　　屏障破坏物，TNBS作为半抗原与肠黏膜角蛋白结合成为全抗原