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Berberine Exerts a Protective Effect on Gut-Vascular Barrier via the Modulation of the Wnt/Beta-Catenin Signaling Pathway During Sepsis

机译:小碱通过败血症期间Wnt /β-Catenin信号通路的调控,对肠血管屏障具有保护作用

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Background/Aims The gut-vascular barrier (GVB) has recently been depicted to dampen the bacterial invasion of the bloodstream. The intestinal mucosa is a tissue rich in small vessels including capillaries. In this study, the protective effect of berberine on GVB in small bowel mucosa was investigated. Methods The rat cecal ligation and puncture (CLP) sepsis model was employed to evaluate the effect of berberine on serum endotoxin level and intestinal vascular permeability to Evans blue in vivo. The rat intestinal microvascular endothelial cells (RIMECs) treated by lipopolysaccharide (LPS) were used to assess the effect of berberine on endothelial permeability to FITC-labeled dextran, transendothelial electrical resistance (TEER), and tight junction (TJ) and adherens junction (AJ) expression in vitro. Results After 24-hr CLP operation the serum endotoxin concentration and gut vascular permeability were significantly increased, while berberine markedly reduced endotoxin level and vascular leakage. In vitro, LPS not only dramatically increased endothelial permeability of RIMECs to FITC-dextran, but also decreased TEER and inhibited claudin-12, beta-catenin and VE-cadherin expression. These effects of LPS were antagonized by berberine. In addition, our in vivo and vitro studies also confirmed that the effect of berberine on GVB could be partially abolished by ICG001. Conclusion Berberine exerted a protective effect on GVB function in sepsis, which was strictly related to the modulation of the Wnt/beta-catenin signaling pathway.
机译:背景/目的最近已经描述了肠血管屏障(GVB)可以抑制细菌入侵血液。肠粘膜是富含毛细血管的小血管的组织。在这项研究中,黄连素对小肠粘膜GVB的保护作用进行了研究。方法采用大鼠盲肠结扎穿刺(CLP)脓毒症模型,评价小ber碱对体内伊文思蓝血清内毒素水平和肠血管通透性的影响。使用脂多糖(LPS)处理的大鼠肠道微血管内皮细胞(RIMEC)评估小ber碱对FITC标记的葡聚糖的内皮通透性,跨内皮电阻(TEER)以及紧密连接(TJ)和粘附连接(AJ)的影响)在体外表达。结果24小时CLP手术后,血清内毒素浓度和肠血管通透性显着升高,而小ber碱显着降低内毒素水平和血管渗漏。在体外,LPS不仅显着增加RIMEC对FITC-葡聚糖的内皮通透性,而且降低TEER并抑制claudin-12,β-catenin和VE-cadherin表达。小ber碱可拮抗脂多糖的这些作用。此外,我们的体内和体外研究还证实,ICG001可以部分消除小ber碱对GVB的作用。结论小Ber碱对脓毒症中GVB的功能具有保护作用,这与Wnt /β-catenin信号通路的调控密切相关。

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