目的研究美沙拉嗪缓释剂对2,4,6-三硝基苯磺酸(2,4,6-trinitro picrylsulfonic acid,TNBS)诱导的溃疡性结肠炎肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6表达的影响,探讨美沙拉嗪缓释剂的抗炎机制。方法应用TNBS/乙醇建立大鼠溃疡性结肠炎模型,实验设正常对照组、模型组、药物治疗组(给予美沙拉嗪溶液100 mg.kg-1.d-1),阳性对照组(给予5-对氨基水杨酸100 mg.kg-1.d-1),每组10只,每天灌胃2次,给药时间从造模后第1天开始至实验结束,共7 d,观察大鼠疾病活动指数(disease index,DAI)、体质量变化及结肠病理学改变,生化法检查大鼠结肠组织髓过氧化物酶(myeloperoxidase,MPO)活性,逆转录聚合酶链反应(Real-time PCR)检测肠组织TNF-α、IL-1β、IL-6mRNA的表达水平。结果与正常对照组比较,模型组大鼠结肠组织MPO活性及TNF-α、IL-1β、IL-6mRNA表达量明显增多(P〈0.05)。与模型组和阳性对照组比较,药物治疗组MPO活性及结肠组织TNF-α、IL-1β、IL-6mRNA的表达明显减少(P〈0.05)。模型组和阳性对照组差异无统计学意义。结论美沙拉嗪缓释剂对大鼠实验性溃疡性结肠炎具有治疗作用,其机制与通过降低中性粒细胞的浸润、抑制促炎因子TNF-α、IL-1β、IL-6mRNA等的表达有关。
Objective To investigate the effects of mesalazine retarder on the expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and interleukin-6(IL-6)in trinitrobenzene sulfonic acid(TNBS)-induced ulcerative colitis(UC) in rats and explore its anti-inflammatory mechanism. Methods UC was induced in rats with TNBS and ethanol.The rats were randomly divided into three groups: normal control(group C),model control(group T),mesalazine retarder treatment group(100 mg·kg-1·d-1)(group M) and 5-ASA treatment group(100 mg·kg-1·d-1)(group A).One day after UC was induced,the rats in the treatment group were intragastric administered mesalazine retarder or 5-ASA every 12 hours for seven days,while the other three groups were taken an intragastric treatment of distilled water.The disease index(DAI),body weight and scores of pathological changes(HS)of rats were calculated.The activity of myeloperoxidase(MPO) was measured by biochemical method,and expressions of TNF-α、IL-1β and IL-6 mRNA were measured by Real-time PCR,respectively. Results Compared with the normal group,the model rats showed significantly increased DAI,HS score and MPO activity in the colon tissues(P0.05),and up-regulated expression of TNF-α、IL-1β and IL-6 mRNA in the colon mucosa(P0.05) as well.Compared with the model and 5-ASA treatment group,mesalazine retarder resulted in a significant reduction in DAI,HS score and MPO activity(P0.05),and lower expression of TNF-α、IL-1β and IL-6 mRNA(P0.05) in the colon mucosa.Compared with the model group,5-ASA treatment group led to a reduction in DAI,HS score and MPO activity,and decreased expression of TNF-α、IL-1β and IL-6 mRNA in the colon mucosa,but no statistic significance was found. Conclusion Mesalazine retarder has protective effect against rat ulcerative colitis,the mechanism of which probably links to reduction of TNF-α,IL-1β and IL-6 expression and neutrophil infiltration.