Effect of serum from patients with severe acute pancreatitis on vascular endothelial permeability

摘要

OBJECTIVE: This study aimed to investigate the effect of serum taken from patients with severe acute pancreatitis (SAP) on vascular endothelial permeability. METHODS: The monolayer permeability of endothelial cells (ECs) was assessed. Morphological changes in ECs, induced by serum from patients with SAP were assessed. Expressions of RhoA, myosin light chain (MLC) phosphorylation, and VE-cadherin protein were detected by Western blot. RESULTS: Compared with the control group, 20% SAP serum significantly increased endothelial monolayer permeability (P < 0.01), markedly induced transcellular F-actin redistribution with stress fiber formation and VE-cadherin derangement with fragmentations located at the cell borders, and increased gaps between ECs. Furthermore, Western blotting showed that SAP serum induced rapid activation of Rho protein, and markedly increased the level of phosphorylated MLC. However, pretreatment with Y-27632 (an inhibitor for Rho kinase) significantly inhibited endothelial hyperpermeability and the morphological changes of F-actin rearrangement and VE-cadherin redistribution. This was associated with a down-regulation of Rho protein expression and a reduction in the level of MLC phosphorylation. CONCLUSIONS: The SAP serum induces the loss of vascular endothelial monolayer integrity, with endothelial F-actin stress fiber formation and VE-cadherin redistribution. One of the mechanisms for this process involves the activation of the Rho/Rho kinase signaling pathway.