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腹泻型肠易激综合征患者结肠黏膜Toll样受体4信号转导通路的研究

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

作者信息

Wang Xue-mei, Liu Yu-lan

机构信息

Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2010 Jun;49(6):491-4.

PMID:20979736
Abstract

OBJECTIVE

To study the expressions of TLR4, CD14, MD-2 and NF-κB 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-κB 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-κB 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-κB 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-κB 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.

摘要

目的

研究腹泻型肠易激综合征(IBS-D)患者结肠黏膜中Toll样受体4(TLR4)、CD14、髓分化蛋白-2(MD-2)及核因子κB(NF-κB)的表达,并与正常受试者进行比较。本研究旨在探讨TLR4及其信号转导通路在IBS-D发病机制中的作用。

方法

分别采用免疫组织化学法检测30例IBS-D患者及12例健康志愿者结肠黏膜中TLR4、CD14、MD-2及NF-κB的表达。分析TLR4的平均吸光度(A值)。研究结肠黏膜CD14、MD-2及NF-κB的阳性表达率。

结果

与健康对照相比,IBS-D患者结肠黏膜中TLR4表达相对于对照显著上调。IBS-D患者TLR4的A值显著更高(0.3971±0.0996比0.3044±0.0481)。IBS-D患者中NF-κB的阳性率和强度显著高于健康者。与对照相比,IBS-D患者固有层中MD-2阳性细胞数量显著增加。IBS-D患者固有层中CD14阳性百分比上调。MD-2和CD14在肠上皮细胞中的表达低或为阴性。

结论

IBS-D患者结肠黏膜中存在TLR4/NF-κB信号转导通路的激活。IBS患者中TLR4表达上调提示其可能与IBS-D的发生有关。

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