TNBS诱导大鼠实验性结肠炎的致病机制

Pathogenesis of TNBS-induced Experimental Colitis in Rats

目的探讨三硝基苯磺酸(TNBS)诱导大鼠实验性结肠炎的致病机制。方法 18只雄性SD大鼠随机分为3组,每组6只:正常组、模型组、美沙拉嗪组。除正常对照组未行造模外,其余两组大鼠均采用TNBS造模。模型组不设干预,正常饮食;美沙拉嗪组给予美沙拉嗪混悬液0.42 g/(kg·d)灌胃;治疗15 d后观察大鼠的结肠病理组织学改变,用免疫组化染色法观察大鼠结肠组织IL-17、β2AR、-βarrestin2、NF-κBp65的表达;用Western blot法检测大鼠脾淋巴细胞β2AR,-βarrestin2和NF-κBp65蛋白的表达;用RT-PCR法检测大鼠结肠组织STAT6 mRNA的表达。结果美沙拉嗪组大鼠的腹泻、黏液脓血便症状得到较快改善,大鼠黏膜组织损伤也明显改善。与正常组相比,模型组大鼠NF-κBp65和STAT6 mRNA表达增多(P<0.01),β2AR和-βarrestin2的表达减少(P<0.01);与模型组比较,美沙拉嗪组大鼠脾淋巴细胞NF-κBp65和STAT6 mRNA表达减少(P<0.01),而β2AR和-βarrestin2的表达增多(P<0.01)。IL-17在正常组和美沙拉嗪组呈低表达,而在模型组呈高表达。结论 IL-17、β2AR、-βarrestin2、NF-κBp65、STAT6在TNBS诱导大鼠实验性结肠炎的致病过程中发挥重要调节作用。

Objective To explore the pathogenesis of TNBS-induced experimental colitis in rats.Methods Eighteen male rats were randomly assigned to the following groups（n=6 each）：mesalazine group,model group,control group.The rats were induced by trinitrobenzene sulfonic acid（TNBS）in model group and mesalazine group.The rats in mesalazine group were given mesalazine（0.42 g/kg body weight every day）through intragastric administration for 15 days.The expression of IL-17,β2AR,β-arrestin2 and NF-κBp65 in ulcerative colonic tissue was observed by immunohistochemical staining.The expression of β2AR,β-arrestin and NF-κBp65 in spleen lymphocytes was analyzed by Western blot.The expression level of STAT6 mRNA in colonic tissue was assayed by RT-PCR.Results The inflammatory symptoms and histological damages of colonic mucosa were obviously alleviated in mesalazine group.As compared with control group,the expression levels of NF-κBp65,STAT6 mRNA and IL-17 were increased（P0.01）,and those of β2AR and β-arrestin2 decreased（P0.01）in model group.After UC model treated with mesalazine,the expression levels of NF-κBp65,STAT6 mRNA and IL-17 were significantly decreased（P0.01）accompanied by significant up-regulation of β2AR and β-arrestin2 expression（P0.01）in mesalazine group.Conclusion IL-17,β2AR,β-arrestin2,NF-κBp65 and STAT6 play an important role in the pathogenesis of TNBS-induced experimental colitis in rats.