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白藜芦醇通过恢复细胞旁渗漏途径中的闭合蛋白和Claudin-5来预防诱导性肠漏。

Resveratrol Prevents -Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway.

作者信息

Lobo de Sá F D, Heimesaat M M, Bereswill S, Nattramilarasu P K, Schulzke J D, Bücker R

机构信息

Medical Department, Division of Gastroenterology, Infectious Diseases, Rheumatology, Nutritional Medicine/Clinical Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Institute of Microbiology, Infectious Diseases, and Immunology, Gastrointestinal Microbiology Research Group, Charité - Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Front Pharmacol. 2021 Apr 15;12:640572. doi: 10.3389/fphar.2021.640572. eCollection 2021.

DOI:10.3389/fphar.2021.640572
PMID:33935732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8082453/
Abstract

is a bacterial human pathogen causing gastroenteritis and sequelae like irritable bowel syndrome. Epidemiologists count the human campylobacteriosis by as the most common foodborne zoonosis and bacterial diarrheal disease worldwide. Based on bioinformatics predictions for potential protective compounds in campylobacteriosis, the question was raised whether the plant-based polyphenol resveratrol is sufficient to attenuate intestinal epithelial damage induced by . We investigated this by performing experimental infection studies in an epithelial cell culture and the secondary abiotic IL-10 mouse model. In -infected human colonic HT-29/B6 cell monolayers, transepithelial electrical resistance (TER) was decreased and the paracellular marker flux of fluorescein (332 Da) increased. Concomitantly, the tight junction (TJ) proteins occludin and claudin-5 were re-distributed off the tight junction domain. This was accompanied by an increased induction of epithelial apoptosis, both changes contributing to compromised barrier function and the opening of the leak pathway induced by . In parallel, the recovery experiments with the application of resveratrol revealed a functional improvement of the disturbed epithelial barrier in both models and . During treatment with resveratrol, TJ localization of occludin and claudin-5 was fully restored in the paracellular domain of HT-29/B6 cells. Moreover, resveratrol decreased the rate of epithelial apoptosis. These resveratrol-induced molecular and cellular effects would therefore be expected to improve epithelial barrier function, thereby minimizing the so-called leaky gut phenomenon. In conclusion, the induction of the leak pathway by and the restoration of barrier function by resveratrol demonstrates its effectiveness as a potential preventive or therapeutic method of mitigating the leaky gut associated with campylobacteriosis.

摘要

是一种引起肠胃炎及肠易激综合征等后遗症的人类细菌性病原体。流行病学家将人类弯曲杆菌病列为全球最常见的食源性人畜共患病和细菌性腹泻病。基于对弯曲杆菌病潜在保护化合物的生物信息学预测,有人提出植物多酚白藜芦醇是否足以减轻由[病原体名称缺失]引起的肠道上皮损伤这一问题。我们通过在一种上皮细胞培养物和继发性非生物白细胞介素 - 10小鼠模型中进行实验性感染研究来对此进行调查。在[病原体名称缺失]感染的人结肠HT - 29/B6细胞单层中,跨上皮电阻(TER)降低,荧光素(332 Da)的细胞旁标记通量增加。同时,紧密连接(TJ)蛋白闭合蛋白和claudin - 5从紧密连接结构域重新分布。这伴随着上皮细胞凋亡诱导增加,这两种变化都导致屏障功能受损以及由[病原体名称缺失]诱导的渗漏途径开放。同时,应用白藜芦醇的恢复实验表明,在两个模型中受干扰的上皮屏障功能都有改善。在用白藜芦醇治疗期间,HT - 29/B6细胞的细胞旁结构域中闭合蛋白和claudin - 5的TJ定位完全恢复。此外,白藜芦醇降低了上皮细胞凋亡率。因此,这些白藜芦醇诱导的分子和细胞效应有望改善上皮屏障功能,从而将所谓的肠漏现象降至最低。总之,[病原体名称缺失]诱导渗漏途径以及白藜芦醇恢复屏障功能证明了其作为减轻与弯曲杆菌病相关的肠漏的潜在预防或治疗方法的有效性。

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