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在葡聚糖硫酸钠诱导的小鼠结肠炎模型中,通过上调紧密连接蛋白和激活Akt/mTOR信号通路来保护肠道屏障功能。

protects intestinal barrier function via upregulation of tight junction proteins and activation of the Akt/mTOR signaling pathway in a mouse model of dextran sodium sulfate-induced colitis.

作者信息

Liu Miao, Xie Wenjie, Wan Xinyue, Deng Tao

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei 430060, P.R. China.

出版信息

Exp Ther Med. 2020 Nov;20(5):10. doi: 10.3892/etm.2020.9138. Epub 2020 Aug 25.

Abstract

, a probiotic, is a gram-positive obligate anaerobic bacillus with acid and heat resistant properties. Previous studies have reported that has beneficial effects in intestinal diseases and regulates intestinal function. The aim of the present study was to investigate the protective effects and mechanisms of on the intestinal barrier function. Mice were randomly divided into three experimental groups (n=15 mice/group), including control, dextran sodium sulfate (DSS) and DSS + . In the DSS and DSS + groups colitis was induced with 3% DSS dissolved in drinking water for 7 days. DSS + group mice were co-treated daily with 200 µl (2x10 CFU) solution via gavage. The intestinal mucosal barrier function in mice was assessed by measuring FITC-labeled 4-kDa dextran (molecular weight, 4,000 Da) flux and by analyzing the expression of tight junction (TJ)-related proteins using western blot analysis. In addition, the secretion levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10 and IL-13, and the concentration of malondialdehyde, glutathione and superoxide dismutase were detected using ELISAs to determine inflammation and oxidative stress, respectively. The activation status of the Akt/mTOR signaling pathway was also investigated using western blot analysis. The results demonstrated that, in mice with DSS-induced colitis treatment, co-treatment with attenuated colitis symptoms and intestinal permeability, increased the expression levels of TJ-related proteins, decreased TNF-α, IL-1β and IL-13 secretion levels but increased those of IL-10, and reduced oxidative stress. Additionally, elevated the phosphorylation of Akt, mTOR and p70 ribosomal protein S6 kinase. Collectively, the present results indicated that protected intestinal barrier function and decreased intestinal mucosal permeability via upregulating the expression levels of TJ-related proteins in a mouse model of DSS-induced colitis. Moreover, the results suggested that the effects of could be mediated by the Akt/mTOR signaling pathway.

摘要

一种益生菌,是一种具有耐酸和耐热特性的革兰氏阳性专性厌氧芽孢杆菌。先前的研究报道,[益生菌名称]在肠道疾病中具有有益作用并调节肠道功能。本研究的目的是探讨[益生菌名称]对肠道屏障功能的保护作用及其机制。将小鼠随机分为三个实验组(每组n = 15只小鼠),包括对照组、葡聚糖硫酸钠(DSS)组和DSS + [益生菌名称]组。在DSS组和DSS + [益生菌名称]组中,用溶解于饮用水中的3% DSS诱导结肠炎7天。DSS + [益生菌名称]组小鼠每天通过灌胃联合给予200 μl(2×10[菌落形成单位数量]CFU)[益生菌名称]溶液。通过测量异硫氰酸荧光素(FITC)标记的4 kDa葡聚糖(分子量4000 Da)通量并使用蛋白质免疫印迹分析来分析紧密连接(TJ)相关蛋白的表达,评估小鼠的肠黏膜屏障功能。此外,使用酶联免疫吸附测定(ELISA)分别检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-10和IL-13的分泌水平以及丙二醛、谷胱甘肽和超氧化物歧化酶的浓度,以确定炎症和氧化应激。还使用蛋白质免疫印迹分析研究Akt/mTOR信号通路的激活状态。结果表明,在DSS诱导的结肠炎小鼠治疗中,联合使用[益生菌名称]可减轻结肠炎症状和肠道通透性,增加TJ相关蛋白的表达水平,降低TNF-α、IL-1β和IL-13的分泌水平,但增加IL-10的分泌水平,并减轻氧化应激。此外,[益生菌名称]提高了Akt、mTOR和p70核糖体蛋白S6激酶的磷酸化水平。总体而言,本研究结果表明,在DSS诱导的结肠炎小鼠模型中,[益生菌名称]通过上调TJ相关蛋白的表达水平保护肠道屏障功能并降低肠黏膜通透性。此外,结果表明[益生菌名称]的作用可能由Akt/mTOR信号通路介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c0/7471846/f71f6a54c8bd/etm-20-05-09138-g00.jpg

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