Emergency Department, Xin Hua Hospital, China.
Pancreas. 2013 May;42(4):633-9. doi: 10.1097/MPA.0b013e318273066b.
This study aimed to investigate the effect of serum taken from patients with severe acute pancreatitis (SAP) on vascular endothelial permeability.
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.
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.
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.
本研究旨在探讨重症急性胰腺炎（SAP）患者血清对血管内皮通透性的影响。
评估内皮细胞（ECs）单层通透性。通过 SAP 患者血清诱导 ECs 的形态变化。通过 Western blot 检测 RhoA、肌球蛋白轻链（MLC）磷酸化和 VE-钙粘蛋白蛋白的表达。
与对照组相比，20%SAP 血清显著增加内皮单层通透性（P < 0.01），明显诱导跨细胞 F-肌动蛋白重排形成应力纤维，并导致 VE-钙粘蛋白排列紊乱，碎片位于细胞边界处，ECs 之间的间隙增大。此外，Western blot 显示 SAP 血清诱导 Rho 蛋白的快速激活，并显著增加磷酸化 MLC 的水平。然而，用 Y-27632（Rho 激酶抑制剂）预处理可显著抑制内皮通透性增加和 F-肌动蛋白重排的形态变化以及 VE-钙粘蛋白重排。这与 Rho 蛋白表达下调和 MLC 磷酸化水平降低有关。
SAP 血清诱导血管内皮单层完整性丧失，内皮 F-肌动蛋白应力纤维形成和 VE-钙粘蛋白重排。该过程的机制之一涉及 Rho/Rho 激酶信号通路的激活。
