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

Cellular Physiology and Biochemistry

Yan He¹ 

关键词: Intestinal mucosa;    Gut-vascular barrier;    Vascular permeability;    Polymicrobial sepsis;    Berberine hydrochloride;    Claudin-12;    VE-cadherin;    Beta-catenin;   

DOI  :  10.1159/000493412

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND