克罗恩病的肠系膜脂肪组织改变与淋巴系统有关。

Mesenteric Adipose Tissue Alterations in Crohn's Disease Are Associated With the Lymphatic System.

机构信息

Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.

出版信息

Inflamm Bowel Dis. 2019 Jan 10;25(2):283-293. doi: 10.1093/ibd/izy306.

DOI:10.1093/ibd/izy306

PMID:30295909

Abstract

BACKGROUND

Mesenteric fat wrapping and thickening are typical characteristics of Crohn's disease (CD). The purpose of this study was to explore the cause of mesenteric adipose hypertrophy and analyze the role of lymphatic vessels in mesenteric adipose tissue in CD.

METHODS

Twenty-three CD patients who underwent ileocolonic resection were included. In CD patients, specimens were obtained from hypertrophic mesenteric adipose tissue (htMAT) next to the diseased ileum. The mesenteric lymphatic vessels in mesenteric adipose tissue were separated under stereoscope microscope. Transmission electron microscopy and immunofluorescence were used to observe the structure of mesenteric lymphatic vessels. The NF-κB signaling pathway in mesenteric adipose tissue was detected in CD specimens using Western blotting.

RESULTS

Electron microscopy showed that the structure of mesenteric lymphatic vessel was discontinuous, and the microstructure of lymphatic endothelial cells appeared ruptured and incomplete. Through an immunofluorescence technique, we found that the surface of lymphatic endothelial cells lacked tight junction protein staining in CD. Also, the expression of claudin-1, occludin, and ZO-1 in the mesenteric lymphatic vessel of htMAT was significantly lower than that of control. These results indicated that the structure of the mesenteric lymphatic vessel in htMAT was mispatterned and ruptured, which could lead to lymph leakage. Leaky lymph factors could stimulate adipose tissue to proliferate. Antigens that leaked into the mesenteric adipose tissue could effectively elicit an immune response. The levels of cytokines (TNF-a, IL-1β, IL-6) was increased in the htMAT of CD patients by activated NF-κB signaling pathway.

CONCLUSIONS

Our findings demonstrated that the hypertrophy of mesenteric adipose tissue may result from mispatterned and ruptured lymphatic vessels. Alteration of mesenteric adipose tissue was associated with activated NF-κB signaling pathway. This study enhances support for elucidating the importance of mesenteric lymphatic vessels and adipose tissue in CD.

摘要

背景

肠系膜脂肪包裹和增厚是克罗恩病（CD）的典型特征。本研究旨在探讨肠系膜脂肪肥大的原因，并分析 CD 中肠系膜脂肪组织中淋巴管的作用。

方法

纳入 23 例行回结肠切除术的 CD 患者。在 CD 患者中，从病变回肠旁的肥大肠系膜脂肪组织（htMAT）获取标本。在立体显微镜下分离肠系膜脂肪组织中的肠系膜淋巴管。使用透射电子显微镜和免疫荧光观察肠系膜淋巴管的结构。使用 Western blot 检测 CD 标本中肠系膜脂肪组织中的 NF-κB 信号通路。

结果

电子显微镜显示肠系膜淋巴管结构不连续，淋巴管内皮细胞的微观结构出现破裂和不完整。通过免疫荧光技术，我们发现 CD 中淋巴管内皮细胞表面缺乏紧密连接蛋白染色。此外，htMAT 肠系膜淋巴管中 Claudin-1、occludin 和 ZO-1 的表达明显低于对照。这些结果表明 htMAT 肠系膜淋巴管的结构模式发生了错误和破裂，这可能导致淋巴液渗漏。渗漏的淋巴因子可刺激脂肪组织增殖。渗漏到肠系膜脂肪组织中的抗原可有效引发免疫反应。通过激活 NF-κB 信号通路，CD 患者 htMAT 中的细胞因子（TNF-a、IL-1β、IL-6）水平增加。