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Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation-induced IBS-like rats 期刊论文

编号：

01d7061b-1a2b-4f95-bfd1-9f31600fd2ec
作者：

Li, Yong#^[1,2]Yang, Tingting^[1];Yao, Qing^[2];Li, Songsong^[3];Fang, En^[3];Li, Yankun^[4];Liu, Chao*^[2]Li, Weimin(李为民)*^[1]
语种：

英文
期刊：

NEUROGASTROENTEROLOGY AND MOTILITY ISSN：1350-1925 2019 年 31 卷 5 期 ; MAY
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关键词：

claudin-4 intestinal permeability irritable bowel syndrome mast cell maternal separation metformin
摘要：

Background Intestinal barrier dysfunction is a key etiologic factor of irritable bowel syndrome (IBS). Metformin improves intestinal barrier function, although the underlying mechanism has yet to be fully explained. This study evaluates the protective effect of metformin on colonic barrier integrity and explores the underlying cellular mechanisms. Methods IBS-like rats were induced by maternal separation. Metformin was administered daily by gavage at 08:30, and rat pups were then separated from their mother. Visceral hyperalgesia and depression-like behaviors were evaluated by colorectal distension, sucrose preference tests, and forced swimming tests. Intestinal integrity was analyzed using sugar probes and transmission electron microscopy. Inflammatory factors and the levels of corticotropin-releasing factor were assessed by PCR and ELISA. The number of mast cells was evaluated by toluidine blue staining. Protein expression and localization were determined using Western blot and immunochemistry. Key Results Metformin pretreatment (a) reduced visceral hypersensitivity to colorectal distension, immobility time and enhanced sucrose consumption; (b) decreased urine lactulose/mannitol ratio and sucralose output; (c) inhibited the dilation of tight junction and prevented claudin-4 translocation; (d) inhibited mast cell activation and downregulated the expression of IL-6, IL-18, tryptase, PAR-2, and ERK activation; (e) inhibited claudin-4 phosphorylation at serine sites and interactions between clau-4 and ZO-1. Conclusions & Inferences Metformin may block mast cell activation to reduce PAR-2 expression and subsequently inhibit ERK activation and clau-4 phosphorylation at serine sites to normalize the interaction of clau-4 and ZO-1 and clau-4 distribution. Metformin may be clinically beneficial for patients with IBS or IBS-like symptoms.
推荐引用方式
GB/T 7714：

Li Yong,Yang Tingting,Yao Qing, et al. Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation-induced IBS-like rats [J].NEUROGASTROENTEROLOGY AND MOTILITY,2019,31(5).
APA：

Li Yong,Yang Tingting,Yao Qing,Li Songsong,&Li Weimin.(2019).Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation-induced IBS-like rats .NEUROGASTROENTEROLOGY AND MOTILITY,31(5).
MLA：

Li Yong, et al. "Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation-induced IBS-like rats" .NEUROGASTROENTEROLOGY AND MOTILITY 31,5(2019).
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