封堵器
炎症性肠病
溃疡性结肠炎
杯状细胞
结肠炎
TLR4型
脂多糖
紧密连接
医学
NF-κB
粘液
肠粘膜
污渍
炎症
免疫学
内科学
病理
生物
上皮
疾病
生物化学
生态学
基因
作者
Taoxiu Xiong,Xiang Zheng,Ke Zhang,Han-Song Wu,Ying‐Jie Dong,Fu-Chen Zhou,Bingbing Cheng,Lin-Zi Li,Wanfeng Xu,Jie Su,Jia-Hui Huang,Zetian Jiang,Bo Li,Beibei Zhang,Gui‐Yuan Lv,Suhong Chen
标识
DOI:10.1016/j.jep.2022.115001
摘要
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), that is associated with a significantly increased risk of colon cancer. As a classic traditional Chinese medicine, Ganluyin (GLY) has a long history as an anti-inflammatory medication, but its impacts on UC has not been established.This study aims to evaluate the protective effect and mechanism of GLY on a pathway involving enteric-origin lipopolysaccharide (LPS), toll-like receptor (TLR)4, and NF-κB in mice with dextran sulfate sodium (DSS)-induced UC.After three weeks of intragastric administration of GLY, a UC model was induced in mice by administration of 4% DSS in drinking water for one week. The disease activity index (DAI) was measured, and histological staining was used to detect histopathological changes of colon. LPS content of the serum was measured by ELISA, and the expression of tight junction proteins and proteins related to TLR4/NF-κB pathway in colon were analyzed by immunohistochemistry or Western Blotting. The intestinal flora was analyzed by 16S rRNA sequencing.GLY improved the histological pathological changes of DSS-induced UC, as assessed by DAI, colonic mucosal damage, inflammatory cell infiltration, and goblet cell and mucus reduction. GLY also protected the intestinal mucosal barrier by increasing the expression of the tight junction proteins, occludin, claudin-1, and ZO-1 and by reducing the serum LPS content and decreasing the expression of TLR4, MyD88, NF-κB, IL-6, IL-1β, and TNF-α proteins in colon. Analyses of the intestinal flora showed that GLY restored the homeostasis of the intestinal flora through increases in the abundance of Firmicutes and decreases in the abundance of Proteobacteria and Bacteroidetes, which is associated with the production of LPS.GLY might exert an anti-UC effect by improving the colonic mucosal barrier and inhibiting the enteric-origin LPS/TLR4/NF-κB inflammatory pathway, and restoring the homeostasis of the intestinal flora in UC mice. These discoveries lay a strong foundation for GLY as a UC treatment.
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