罗格列酮治疗实验性小鼠结肠炎疗效观察

Effect of Rosiglitazone on Experimental Colitis of Mice

背景:溃疡性结肠炎病程迁延巨传统内外科治疗效果均不理想,寻找新型而有效的药物一直是该领域研究的热点。目的:观察过氧化物酶体增生物激活受体（PPAR）-r配体罗格列酮治疗葡聚糖硫酸钠（DSS）诱导小鼠结肠炎的疗效。方法:小鼠自由饮用5％DSS 7天产生急性炎症模型,有半稀便、腹泻、大便隐血（+）和肉眼血便症状之一者纳入研究,此后继续饮用自来水14天产生慢性炎症模型。实验动物分为预防组、急性炎症组和慢性炎症组3组,各组再分为实验组（罗格列酮治疗）、对照组1（柳氮磺胺吡啶治疗）和对照组2（甲基纤维素治疗）。观察指标包括疾病活动指数（DAI）、结肠组织学评分、结肠上皮p65（免疫组化法）和肿瘤坏死因子（TNF）-αmRNA（原位杂交法）的表达。结果:罗格列酮能减少DSS诱导结肠炎的DAI和结肠组织学评分,同时降低结肠上皮p65和TNF-αmRNA的表达。结论:罗格列酮能有效预防和缓解DSS诱导的小鼠结肠炎,其作用机制可能包括抑制促炎症因子的表达。

Background: Ulcerative colitis is a chronic disease, and the results of traditional medical and surgical therapy is not satisfied. So looking for a new and more effective drug has always been the focus in this field. Aims: To investigate the effect of peroxisome proliferator-activated receptor (PPAR)-r li-gand rosiglitazone on dextran sulfate sodium (DSS)-induced colitis of mice. Methods: Acute colitis was induced by feeding with 5% DSS for 7 days and chronic colitis by drinking water in the following 14 days in mice. The mice were selected for the investigation in presence of one of the following symptoms: loose stool, diarrhea, hemoccult (+) and gross bleeding, and were divided into three groups: prophylactic group, therapeutic group during the acute phase and therapeutic group during the chronic phase of the disease. Each group included three subgroups: rosiglitazone-treated, salicylazosulfapyri-dine (SASP)-treated and vehicle-treated. Four indices were used for evaluation: disease activity index (DAI), colonic histologic score, expression of p65 protein and tumor necrosis factor (TNF)-α mRNA in the colonic epithelium. The expression of p65 was examined by immunohistochemistry, the TNF-α mRNA by hybridization in situ. Results: Treatment with rosiglitazone could significantly reduce the DAI and colonic histologic scores of DSS-induced colitis. The expression of p65 and TNF-α mRNA in the colonic mucosa also reduced. Conclusions: Rosiglitazone is effective in preventing and relieving the DSS-induced colitis. Inhibition of the pro-inflammatory factors may be involved in its mechanism.