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法尼酯X受体在显微镜下结肠炎中的表达:在疾病病因发病机制中的潜在作用

Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis.

作者信息

Torres Joana, Palmela Carolina, Gomes de Sena Pedro, Santos Maria Pia Costa, Gouveia Catarina, Oliveira Maria Helena, Henriques Ana Raquel, Rodrigues Cecília, Cravo Marília, Borralho Paula

机构信息

Gastroenterology Department, Hospital Beatriz Ângelo, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.

Pathology Department, Hospital Beatriz Ângelo, Loures, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.

出版信息

GE Port J Gastroenterol. 2018 Jan;25(1):30-37. doi: 10.1159/000481197. Epub 2017 Oct 11.

Abstract

INTRODUCTION

Microscopic colitis (MC) is a chronic inflammatory bowel disease with unclear etiology. Bile acid (BA) malabsorption has been described in MC patients. Farnesoid X receptor (FXR) is the main BA receptor; FXR-mediated mechanisms prevent the noxious effects of BA accumulation, preserving the integrity of the intestinal epithelial barrier and preventing intestinal inflammation.

AIM

Our aim was to describe the expression of FXR in patients with MC.

METHODS

Archival formalin-fixed paraffin-embedded samples from the terminal ileum, right and left colon were obtained from patients with MC and matched controls. Immunohistochemistry was performed and nuclear FXR expression scored in a semi-quantitative way.

RESULTS

169 formalin-fixed paraffin-embedded samples from 35 patients with MC and 31 controls were retrieved. There was a significant reduction of FXR expression in patients with MC versus controls both in the right colon (moderate-strong FXR expression: 21.1 vs. 64.3%; = 0.003) and left colon (moderate-strong FXR expression: 8.3 vs. 38.7%; = 0.027). No significant differences in FXR expression were observed in the ileum of patients with MC (moderate-strong FXR expression: 76.9 vs. 90.9%; = 0.5). We found no difference in FXR expression between the two types of MC. No association between the degree of lymphocyte infiltration or the thickness of collagen band and FXR expression was found.

CONCLUSIONS

Patients with MC present a significantly lower expression of FXR in the colon. This could render colonic epithelial cells more susceptible to the deleterious effects of BA, contributing to disease pathogenesis and symptoms in MC.

摘要

引言

显微镜下结肠炎(MC)是一种病因不明的慢性炎症性肠病。MC患者中已发现胆汁酸(BA)吸收不良。法尼酯X受体(FXR)是主要的BA受体;FXR介导的机制可防止BA积累的有害影响,维持肠道上皮屏障的完整性并预防肠道炎症。

目的

我们的目的是描述MC患者中FXR的表达情况。

方法

从MC患者和匹配的对照中获取来自回肠末端、右结肠和左结肠的存档福尔马林固定石蜡包埋样本。进行免疫组织化学,并以半定量方式对核FXR表达进行评分。

结果

从35例MC患者和31例对照中检索到169个福尔马林固定石蜡包埋样本。与对照组相比,MC患者右结肠(中度 - 强FXR表达:21.1%对64.3%;P = 0.003)和左结肠(中度 - 强FXR表达:8.3%对38.7%;P = 0.027)中FXR表达显著降低。在MC患者的回肠中未观察到FXR表达的显著差异(中度 - 强FXR表达:76.9%对90.9%;P = 0.5)。我们发现两种类型的MC之间FXR表达无差异。未发现淋巴细胞浸润程度或胶原带厚度与FXR表达之间存在关联。

结论

MC患者结肠中FXR表达显著降低。这可能使结肠上皮细胞更容易受到BA的有害影响,从而导致MC的疾病发病机制和症状。

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