Toll样受体4、核因子-b通路在溃疡性结肠炎发病机制中的应用

    The research of the role of Toll-like receptor 4 and nuclear factor-b pathway in the pathogenesis of ulcerative colitis

    • 摘要: 目的:通过研究Toll样受体4(Toll-like receptor,TLR4)、髓样分化分子88(myeloid differentiation factor,Myd88)、核因子-b(nuclear factor-b,NF-b)在溃疡性结肠炎(ulcerative colitis,UC)大鼠模型结肠组织中的表达以及外周血中白细胞介素1(interleukin-1,IL-1)的表达水平,探讨TLR4/NF-b信号通路在UC发病中的作用。方法:将健康SD大鼠40只随机分为模型组(A组)和正常对照组(B组),每组各20只,运用复合法(三硝基苯磺酸+乙醇)制备细胞免疫反应性UC大鼠模型,造模成功后,进行大体形态损伤评分,HE染色观察大鼠结肠黏膜组织学改变,采用RT-PCR法检测UC各组大鼠结肠黏膜组织中TLR4、Myd88和NF-b表达,采用ELISA法检测外周血中IL-1的表达。结果:与B组比较,A组大鼠结肠黏膜大体形态评分、组织学损伤评分、结肠黏膜组织中TLR4、Myd88和NF-b的表达及外周血中IL-1的表达均显著增高(P0.01)。结论:UC大鼠模型中TLR4、Myd88、NF-b和IL-1的表达明显升高,TLR4可能通过介导NF-b引发信号通路下游的基因表达,从而导致炎症因子的释放。

       

      Abstract: Objective:To explore the expression of the Toll-like receptor 4(TLR4),myeloid differentiation factor-88(Myd88) and nuclear factor-b(NF-b) and interleukin-1(IL-1) in colon tissue and peripheral blood of ulcerative colitis(UC) rat model and determine the role of TLR4/NF-b signaling pathway on the pathogenesis of UC, and provide new ideas to know the development of UC rat and therapy using pathway blocking drugs. Methods:Forty Sprague-Dayley(SD) rats were randomly divided into Group A(the model group,20 rats) and Group B(the control group,20 rats). The model of UC rats with cell immunoreactivity were made using compound method(Trinitrobenzene sulfonic acid and ethanol),which were evaluated by histology injury and HE staining of colonic mucosa. The expression of TLR4,Myd88 and NF-b of colonic mucosa were detected by using RT-PCR, and the expression levels of IL1 in sera were detected by ELISA. Results:Compared with Group B, the histopathologic changes, macroscopical changes and the expression of TLR4,Myd88,NF-b in colonic mucosa and IL-1 levels in sera of Group A were significant higher(P 0. 01). Conclusions:The expression of TLR4,Myd88 and NF-b in the colonic mucosa of UC rat is significant higher than that in normal group and TLR4 expression may induce the expression of NF-b mRNA of its downstream genes, which can lead to the release of inflammatory cytokines.

       

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