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半乳糖寡糖通过调节肠道菌群和抑制 NF-κB 通路来预防 DSS 诱导的小鼠结肠炎。

Galactooligosaccharides protects against DSS-induced murine colitis through regulating intestinal flora and inhibiting NF-κB pathway.

机构信息

Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Translational Medicine Center, Beijing Chest Hospital, Capital Medical University, Beijing 101149, PR China; Beijing Key Laboratory in Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, PR China.

Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China.

出版信息

Life Sci. 2020 Feb 1;242:117220. doi: 10.1016/j.lfs.2019.117220. Epub 2019 Dec 24.

Abstract

BACKGROUND/AIMS: Previous studies have demonstrated that Galactooligosaccharides (GOS), known as "bifidus factor", has anti-inflammatory effects. Colitis, a kind of colonic inflammatory damage could be induced by different chemicals. The pathogenesis and mechanism of colitis remains unclear, and may be related to intestinal microflora, genetic susceptibility or immune factors. The aim is to explore the effects of GOS on intestinal flora and its anti-inflammatory effects in Dextran Sulfate Sodium (DSS) induced murine colitis and extrapolate the underlying mechanism.

MAIN METHODS

Initially, 5% DSS was used to induced colitis by free access to drinking water for 5-7 days. Then the mice were treated with GOS 1 day after DSS treatment. Colon samples were evaluated grossly using a microscope. The percentage of Treg and Th17 cells was analyzed by flow cytometry. The levels of cytokines secretion and mRNA expression were detected by ELISA and real-time PCR. The level of protein was detected by western blot.

KEY FINDINGS

GOS attenuated DSS induced body weight loss and also reduced the increase in disease index caused by DSS. GOS ameliorated DSS induced colonic histological damage. The protective effect of GOS on DSS induced colitis may be partly attributed to intestinal flora regulation and Th17/Treg imbalance. Furthermore, GOS markedly decreased cytokines (IL-6, IL-18, IL-13 and IL-33) secretion and mRNA expression in colon tissues, through inhibiting activation of NF-κB pathways.

SIGNIFICANCE

GOS could prevent the DSS induced colitis through intestinal flora regulation and reduce the secretion of inflammation related cytokines relying on the NF-κB signaling pathway.

摘要

背景/目的:先前的研究表明,半乳糖寡糖(GOS),被称为“双歧因子”,具有抗炎作用。结肠炎是一种结肠炎症损伤,可以由不同的化学物质引起。结肠炎的发病机制和机制尚不清楚,可能与肠道菌群、遗传易感性或免疫因素有关。目的是探讨 GOS 对肠道菌群的影响及其在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎中的抗炎作用,并推断其潜在机制。

主要方法

最初,通过自由饮用 5%的 DSS 溶液 5-7 天来诱导结肠炎。然后,在 DSS 处理后 1 天用 GOS 处理小鼠。使用显微镜对结肠样本进行大体评估。通过流式细胞术分析 Treg 和 Th17 细胞的百分比。通过 ELISA 和实时 PCR 检测细胞因子分泌和 mRNA 表达水平。通过 Western blot 检测蛋白水平。

主要发现

GOS 减轻了 DSS 诱导的体重减轻,也降低了 DSS 引起的疾病指数的增加。GOS 改善了 DSS 诱导的结肠组织学损伤。GOS 对 DSS 诱导的结肠炎的保护作用可能部分归因于肠道菌群的调节和 Th17/Treg 失衡。此外,GOS 明显降低了结肠组织中细胞因子(IL-6、IL-18、IL-13 和 IL-33)的分泌和 mRNA 表达,通过抑制 NF-κB 通路的激活。

意义

GOS 可以通过调节肠道菌群和依赖 NF-κB 信号通路减少炎症相关细胞因子的分泌来预防 DSS 诱导的结肠炎。

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