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抗 TNF 治疗诱导炎症性肠病患者黏膜基因表达变化。

Mucosal gene expression changes induced by anti-TNF treatment in inflammatory bowel disease patients.

机构信息

National Institute of Pathology "Victor Babeş", Bucharest, Romania.

"Fundeni" Clinical Institute, Bucharest, Romania.

出版信息

Drug Dev Res. 2019 Sep;80(6):831-836. doi: 10.1002/ddr.21566. Epub 2019 Jul 19.

DOI:10.1002/ddr.21566
PMID:31322753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6790597/
Abstract

In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.

摘要

在过去的二十年中,抗肿瘤坏死因子(anti-TNF)疗法已被广泛用于诱导和维持炎症性肠病(IBD)的临床和内镜缓解,从而彻底改变了该疾病的治疗方法。在这项研究中,我们旨在比较接受 5-氨基水杨酸(5-ASA)(N = 25)或抗 TNF 药物(N = 12)治疗的克罗恩病和溃疡性结肠炎患者的炎症黏膜与无药物治疗的 IBD 患者(N = 12)和非 IBD 对照者(N = 18)之间的基因表达变化。通过 qPCR 评估了 84 个先前与 IBD 相关的基因的黏膜表达。我们发现,两种治疗方案均会降低 LCN2、NOS2 和 TFF1 的表达水平,与非 IBD 对照者相比,无药物治疗的患者中这些基因的表达水平升高。有趣的是,抗 TNF 药物对 LCN2 和 TFF1 水平的影响更强。然而,5-ASA 似乎会诱导 NOS2 表达的更明显降低。此外,我们发现抗 TNF 治疗可显著增加 ABCB1 的表达,使其水平与非 IBD 对照者相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c3/6790597/4931afdef33a/DDR-80-831-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c3/6790597/4931afdef33a/DDR-80-831-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c3/6790597/4931afdef33a/DDR-80-831-g001.jpg

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本文引用的文献

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Int J Mol Sci. 2019 Apr 9;20(7):1755. doi: 10.3390/ijms20071755.
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Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn's Disease and Ulcerative Colitis.克罗恩病和溃疡性结肠炎的肠道黏膜差异转录组学生物标志物。
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The importance of the polymorphisms of the ABCB1 gene in disease susceptibility, behavior and response to treatment in inflammatory bowel disease: A literature review.
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