Toll样受体(TLR)2、TLR4和TLR9在大鼠结肠炎模型结肠组织中的表达及其意义  

Expression and Significance of Toll-like Receptor (TLR) 2, TLR4 and TLR9 in Colonic Mucosa of Rat Model with Induced Colitis

作　　者：陈胜[1] 邹开芳[1] 杨天[2] 谭琰[1] 丁炎波[3] 钱伟[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院消化内科,430022 [2]南京市鼓楼医院消化内科 [3]常州市第一人民医院消化内科

出　　处：《胃肠病学》2007年第6期339-343,共5页Chinese Journal of Gastroenterology

摘　　要：背景:Toll样受体(TLRs)家族可能在一系列免疫性疾病中发挥重要作用。目的:观察TLR2、TLR4和TLR9在大鼠结肠炎模型结肠组织中的表达,探讨三者在炎症性肠病(IBD)发病机制中的作用。方法:以三硝基苯磺酸(TNBS)+乙醇灌肠制备大鼠结肠炎模型,观察和评估结肠黏膜的大体和组织学变化。分别以黄嘌呤氧化酶法和紫外分光光度法测定超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性;以免疫组化方法检测TLR2、TLR4和TLR9的表达,以逆转录聚合酶链反应(RT-PCR)检测三者mRNA的表达。结果:造模后结肠组织中可见大量炎性细胞浸润,累及黏膜下层和固有层。与正常对照组相比,模型组结肠组织SOD活性显著降低(P<0.01),MPO活性显著升高(P<0.01)。正常对照组结肠黏膜下层和固有层炎性细胞胞膜和胞质仅有少量TLR2、TLR4表达,未见TLR9表达;模型组三者表达均显著增加(P<0.01),此外还可见TLR2表达于肠上皮近肠腔侧胞膜,TLR4表达于肠上皮近肠腔侧胞膜和腺上皮近腺腔侧胞膜。模型组结肠组织可见TLR2、TLR4、TLR9 mRNA表达,而正常对照组未检出三者mRNA的表达。TLR2、TLR4、TLR9的表达与MPO活性呈正相关(P<0.05),与SOD活性呈负相关(P<0.01)。结论:大鼠结肠炎模型结肠组织中TLR2、TLR4和TLR9表达明显增加,可能与结肠的自身免疫损伤有关。Background： Toll-like receptors （TLRs） family may play important roles in the pathogenesis of many immunologic diseases. Aims： To investigate the expression of TLR2, TLR4 and TLR9 in the colonic mucosa of rat model with induced colitis and their roles in the pathogenesis of inflammatory bowel disease （IBD）. Methods： Colitis was induced in the rat model by trinitrobenzene sulfonic acid （TNBS） and ethanol enema. The macroscopic and histological changes of colonic mueosa were observed and evaluated. Activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） were measured by xanthine oxidase method and ultraviolet spectrophotometry, respectively. Expression of TLR2, TLR4 and TLR9 were determined by immunohistochemistry and levels of TLR2, TLR4 and TLR9 mRNA by reverse transcriptase polymerase chain reaction （RT-PCR）. Results： Infiltration with large number of inflammatory cells were observed in colonic submucosa and lamina propria of the model group. Compared with the normal control group, activity of SOD in colonic mucosa decreased significantly （P〈0.01） and activity of MPO increased significantly （P〈0.01） in the model group. In the normal control group, slight expression of TLR2 and TLR4 was observed in the cellular membrane and cytoplasm of inflammatory cells in submucosa and lamina propria, no expression of TLR9 was observed, whereas expression of TLR2, TLR4 and TLR9 increased significantly （P〈0.01） in the model group. In addition, TLR2 expression also could be observed in luminal side membrane of colonic epithelium and TLR4 in luminal side membrane of both colonic epithelium and glandular epithelium in the model group. TLR2, TLR4 and TLR9 mRNA were increased in the model group but absent in the normal control group. Expression of TLR2, TLR4 and TLR9 correlated positively with MPO activity （P〈0.05） but negatively with SOD activity （P〈0.01）. Conclusions： Expression of TLR2, TLR4 and TLR9 increase significantly in the colonic mucosa of rat mode

关 键 词：TOLL样受体 炎性肠疾病 自身免疫 

分 类 号：R574[医药卫生—消化系统]