腹泻型肠易激综合征患者结肠黏膜Toll样受体4信号通路的研究

An investigation of signal transduction pathway of colonic mucosal toll-like receptor 4 in patients with diarrhea-irritable bowel syndrome

目的 研究Toll样受体4（TLR4）、CD14、髓样分化蛋白-2（MD-2）及NF-κB在腹泻型肠易激综合征（IBS-D）患者结肠黏膜的表达,了解TLR4/NF-κB信号传导通路及其在IBS致病机制中的作用.方法 采用免疫组化法半定昔分析30例IBS-D患者及12名健康志愿者结肠黏膜TLR4、CD14MD-2和NF-κB的表达情况.结果 免疫组化结果显示,IBS-D组TLR4的吸光度[A值,（0.3971±0.0996）]高于健康对照组（0.3044±0.0481）;IBS-D组的NF-κB阳性率及强度均比健康对照组增高;IBS-D组的黏膜固有层MD-2阳性细胞数高于健康对照组,固有层CD14阳性率高于健康对照组,差异均有统计学意义.两组的肠上皮细胞中MD-2和CD14均为低表达或无表达.结论 IBS-D患者的肠道黏膜存在TLR4/NF-κB信号传导通路的活化,TLR4在IBS-D发病中具有一定作用.

Objective To study the expressions of TLR4, CD14, MD-2 and NF-kB in colonic mucosa in patients with diarrhea-irritable bowel syndrome （IBS-D） , and compared with normal subjects. The purpose of this study is to explore the role of TLR4 and TLR4 signal transduction pathway in the pathogenesis of IBS-D. Methods The expressions of TLR4, CD14, MD-2 and NF-kB in colon mucosa were examined by immunohistochemistry （IHC） in 30 IBS-D patients and 12 healthy volunteers separately. The average absorbance （A value） of TLR4 was analyzed. The positive expression rates of CD14, MD-2 and NF-kB of colonic mucosa were studied. Results Compared with healthy controls, significant upregulation of TLR4 expression relative to controls was found in colon mucosa of IBS-D. A value of TLR4 in IBS-D was significantly higher （0.3971 ±0.0996 vs 0. 3044 ±0.0481）. The positive rate and intensity of NF-kB in IBS-D were significantly higher than those in healthy. The number of positive cells of MD-2 showed significant increase in lamina propria of IBS-D against controls. The percent of CD14 positive was upregulated in lamina propria in IBS-D. The expressions of MD-2 and CD14 in intestine epithelial cell were low or negative. Conclusions There is the activation of the signal transduction pathway of TLR4/NF-kB in the colonic mucosa of patients with IBS-D. Up-regulated expression of TLR4 in IBS patients suppose that it might contribute to occurrence of IBS-D.