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溃疡性结肠炎患者结肠黏膜中Toll样受体TLR2、TLR4和TLR9的表达及意义

Expression and implication of toll-like receptors TLR2, TLR4 and TLR9 in colonic mucosa of patients with ulcerative colitis.

作者信息

Tan Yan, Zou Kai-Fang, Qian Wei, Chen Sheng, Hou Xiao-Hua

机构信息

Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Gastroenterology, Affiliated Hospital of Hainan Medical College, Haikou, 570102, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2014 Oct;34(5):785-790. doi: 10.1007/s11596-014-1353-6. Epub 2014 Oct 16.

Abstract

Toll-like receptors (TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis (UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC (at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction (RT-PCR). The disease activity index (DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group (P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity.

摘要

Toll样受体(TLRs)家族可能在炎症性肠病中发挥重要作用。本研究检测了溃疡性结肠炎(UC)患者结肠组织中TLR2、TLR4和TLR9的表达,并探讨了它们在UC发病机制中的作用。在结肠镜检查期间,从30例轻度或中度UC患者(活动期)的结肠及10例健康对照者的结肠获取活检组织。采用免疫组织化学方法检测TLR2、TLR4和TLR9蛋白表达水平。通过逆转录聚合酶链反应(RT-PCR)评估TLR2、TLR4和TLR9的mRNA表达水平。测定疾病活动指数(DAI)、结肠镜和组织学分级以及粪便微生物菌群。组织学检查显示,UC患者的肠黏膜发生急性炎症改变。免疫组织化学显示,UC患者结肠上皮和炎症细胞中TLR2、TLR4和TLR9的表达水平高于对照组(P<0.01)。UC患者中TLR2、TLR4和TLR9的mRNA表达水平升高,但在正常对照中未检测到。TLR2、TLR4和TLR9的表达水平呈正相关,且与DAI、结肠镜和组织学分级以及粪便微生物菌群密切相关。UC的一个重要机制可能是肠道菌群失调导致黏膜免疫异常激活,引起介导固有免疫的TLRs失调。

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