Toll样受体4及其负性调控因子Tollip在结肠炎大鼠肠黏膜中的表达  

Expression of Toll-like receptor 4 and its negative regulating factor Tollip in colonic mucosa of rats with experimental colitis

作　　者：徐宁[1] 于振海[2,3] 王志强[2] 曲洪林[2] 孙毅[2] 刘蛟[2] 

机构地区：[1]青岛大学医学院附属烟台毓璜顶医院消化内科,烟台264000 [2]滨州医学院人体解剖学教研室,滨州256603 [3]第二军医大学基础部人体解剖学教研室,上海200433

出　　处：《第二军医大学学报》2012年第1期32-37,共6页Academic Journal of Second Military Medical University

基　　金：山东省自然科学基金(ZR2009CL006)~~

摘　　要：目的探讨Toll样受体4(TLR4)、NF-κB p65及负性调控因子Tollip在三硝基苯磺酸(TNBS)诱导的结肠炎大鼠肠黏膜中的表达。方法 40只健康雄性SD大鼠随机分为正常对照组和模型组。采用免疫组织化学及RT-PCR方法比较两组大鼠肠黏膜TLR4、NF-κB p65和Tollip的表达。结果 TLR4、NF-κB p65mRNA在模型组肠黏膜中的表达高于正常对照组(TLR4:0.376±0.029vs 0.215±0.049,t=2.731,P=0.013;NF-κB p65:0.746±0.049vs 0.206±0.063,t=6.055,P=0.000),与大体形态损伤评分(TLR4:r=0.754,P=0.000;NF-κB p65:r=0.548,P=0.012)及组织学损伤评分(TLR4:r=0.866,P=0.000;NF-κB p65:r=0.919,P=0.000)呈正相关。Tollip mRNA在模型组及正常组中表达差异无统计学意义(0.288±0.050vs 0.140±0.046,t=1.993,P=0.061);Tollip蛋白在模型组肠黏膜固有层的表达高于正常组;Tollip的表达与大体形态损伤评分(r=-0.497,P=0.026)及组织学损伤评分(r=-0.551,P=0.012)呈负相关。结论 Toll样受体4与负性调控因子Tollip的表达失衡参与了炎症性肠病的发病机制。Objective To investigate the expression of Toll-like receptor 4 （TLR4）, NF-κB p65 and the negative regulating factor Toll-interacting protein （Tollip） in colonic mucosa of rats with 2,4,6-trinitrobenzene sulfonic acid （TNBS）- induced experimental colitis. Methods Forty healthy male SD rats were randomly divided into normal control group and model group. The expression of TLR4, NF-κBp65 and Tollip was detected and compared between the two groups by immunohistochemistry（IHC） and RT-PCR. Results RT-PCR revealed a significant higher expression of TLR4 and NF-κB p65 mRNA in the model group compared with the normal control group （TLR4： 0. 376±0. 029 vs 0. 215±0. 049, t= 2. 731, P=0.013;NF-κBp 65： 0.746±0.049 vs0.2064±0.063, t=6.055, P=0.000）. The expression of TLR4 and NF-κBp65 was positively correlated with the general injury score （TLR4： r= 0. 754, P= 0. 000; NF-κB p65： r = 0. 548, P= 0. 012） and the histological injury score （TLR4： r=0. 866, P=0. 000： NF-κB p65： r=0. 919, P=0. 000）. Expression of Totlip mRNA was not significantly different between the two groups as detected by RT-PCR （0. 2884±0. 050 vs 0. 140±0. 046, t= 1. 993, P= 0. 061）. IHC revealed that Tollip protein expression was mainly assembled in the colonic mucosal lamina propria, and the expression in the model group was higher than that in the normal control group. Tollip expression was negatively correlatedwith the general injury score （r=-0. 497, P= 0. 026） and the histological injury score （r= -0. 551,P= 0. 012）. Conclusion The unbalanced expression of TLR4 and the negative regulating factor Tollip participates in the pathogenesis of inflammatory bowel disease.

关 键 词：TOLL样受体4 NF-ΚB P65 Tollip 结肠炎 肠黏膜 

分 类 号：R574.62[医药卫生—消化系统]