Salvianolic acid B ameliorates lipopolysaccharide‐induced albumin leakage from rat mesenteric venules through Src

Abstract

Lipopolysaccharide (LPS) causes microvascular barrier disruption, leading to albumin leakage from microvessels resulting in a range of disastrous sequels. Salvianolic acid B (SalB) is a major water‐soluble component derived from Salvia miltiorrhiza. The present study was intended to investigate the impact of SalB on endothelial cell barrier in vivo in rat mesenteric venules as well as in vitro in human umbilical vein endothelial cells (HUVECs). Male Wistar rats were challenged by infusion of LPS (2 mg/kg/h) through left femoral vein for 90 min. SalB (5 mg/kg/h) was administrated either simultaneously with LPS or 30 min after LPS infusion through the left jugular vein. Caveolae in venular walls were observed by electron microscopy. HUVECs were incubated with LPS with or without SalB. The expression of Zonula occluden‐1 (ZO‐1), VE‐cadherin, caveolin‐1 and Src in HUVECs was assessed by Western blot and confocal microscopy, binding of SalB to Src was measured using Surface Plasmon Resonance and BioLayer Interferometry. Treatment with SalB inhibited albumin leakage from rat mesenteric venules and inhibited the increase of caveolae number in venular endothelial cells induced by LPS. In addition, SalB inhibited the degradation of ZO‐1, the phosphorylation and redistribution of VE‐cadherin, the expression and phosphorylation of caveolin‐1, and phosphoirylation of Src in HUVECs exposed to LPS. Furthermore, SalB was found able to bind to Src. This study demonstrates that protection of SalB against microvascular barrier disruption is a process involving both para‐ and trans‐endothelial cell pathway, and highly suggests Src as the key enzyme for SalB to work.