Microvascular Reviews and Communications
Online ISSN : 1880-5906
Print ISSN : 2188-1707
ISSN-L : 2188-1707
Salvianolic acid B binds to Src and ameliorates mesenteric venules hyperpermeability in endotoxmia rats
Chun-Shui PanYing-Hua LiuYu-Ying LiuYu ZhangKe HeXiao-Yuan YangBai-He HuXin ChangXiao-Hong WeiJing-Yu FanJing-Yan Han
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2014 Volume 7 Issue 1 Pages 36a

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Abstract

Background: Microvascular hyperpermeability is a crucial contributor to the gastrointestinal injury, for which the current clinical therapy remains unsatisfied. Src regulates the hyperpermeability-related proteins, such as caveolin-1, VE-cadherin and ZO-1. This study aimed to evaluate whether salvianolic acid B (SalB) binds to Src to regulate caveolin-1, VE-cadherin and ZO-1, to ameliorate mesenteric venules hyperpermeability in endotoxmia rats.

Methods: The male Wistar rats were challenged by infusion of LPS (2mg/kg/h) for 90 min, with or without SalB (5mg/kg/h). Human umbilical vein endothelial cells (HUVECs) were incubated with LPS or/and SalB. Microcirculation was assessed by intravital microscopy, caveolae in microvascular endothelial cells by electron microscopy, endothelial cell junctional proteins, caveolin-1 and Src by Western blot and confocal microscopy, and the interaction of Src and SalB by Surface Plasmon Resonance (SPR) and BioLayer Interferometry (BLI).

Results: SPR and BLI demonstrated that SalB was able to bind to Src in a dose-dependent manner, further to inhibit the phosphorylation of Src, caveolin-1 and vascular endothelial cadherin increased in human umbilical vein endothelial cells, to restore the distribution of Zonula occluden-1 and VE-cadherin degradated in cells exposed to LPS. Furthermore, SalB alleviated the inclement of caveolae in microvascular venules, and the evoked albumin leakage from venules in endotoxmia rat mesentery.

Conclusions: SalB prevents endothelial barrier dysfunction and hyperpermeability via binding to Src to inhibit the activity of Src. These findings identify SalB as a promising approach to permeability, and indicate Src as novel target for hyperpermeability treatment.

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© 2014 by Japanese Society for Microcirculation
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