TNBS诱导大鼠实验性结肠炎的致病机制

摘要

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、β-arrestin2、NF-κBp65的表达;用Western blot法检测大鼠脾淋巴细胞β2AR,β-arrestin2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β-arrestin2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β-arrestin2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、β-arrestin2、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 TNBSinduced experimental colitis in rats. Methods Fighteen 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 1L-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-βBp65 , STAT6 mRNA and 1L-17were increased ( P＜0. 01) , and those of β2AR and β-arrestin2 decreased ( P＜0. 0l)in model group. After UC model treated with mesalazine , the expression levels of NF-κBp65 , STAT6 mRNA and IL-17 were significantly decreased ( P＜0. 01) accompanied by significant up-regulation of β2 AR and β-arrestin2 expression ( P＜ 0. 01 ) in mesalazine group. Conclusion IL-17 , β2 AR , β-arrestin2 ,NF-κBp65 and STAT6 play an important role in the pathogenesis of TNBS-induced experimental colitis in rats.