Ebihara Itaru, Hirayama Kouichi, Nagai Miho, Koda Megumi, Gunji Masanobu, Okubo Yuki, Katayama Taisuke, Sato Chihiro, Usui Joichi, Yamagata Kunihiro, Kobayashi Masaki
Department of Nephrology, Mito Saiseikai General Hospital, Mito, Japan.
Ther Apher Dial. 2014 Jun;18(3):272-8. doi: 10.1111/1744-9987.12215.
Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)-induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans-endothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1 ± 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 ± 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE-cadherin levels remained unchanged during PMX-DHP therapy. There was no significant difference in serum soluble VE-cadherin levels before PMX-DHP therapy between survivors and non-survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX-DHP therapy. There was no correlation between soluble VE-cadherin levels and clinical data, except white blood cell count (r = -0.277, P = 0.0009). There was no correlation between soluble VE-cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE-cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE-cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE-cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.
毛细血管通透性是所有器官床微循环中受到严格调控的一个特性；然而，在脓毒症中这一特性会发生根本性改变。有几种分子被作为与毛细血管通透性相关的因素进行研究，并且血管内皮生长因子（VEGF）通过VEGF受体诱导的信号传导导致血管内皮（VE）-钙黏蛋白内化，进而导致血管内皮细胞分离增加和跨内皮通透性增加。我们研究了脓毒症患者血清中可溶性VE-钙黏蛋白水平。采用酶联免疫吸附测定法测量47例接受多黏菌素B固定纤维柱直接血液灌流（DHP-PMX）治疗的脓毒症患者血清中可溶性VE-钙黏蛋白水平。接受PMX-DHP治疗前脓毒症患者血清可溶性VE-钙黏蛋白水平为3424.1±2033.0 ng/mL，显著低于对照组（5862.0±1521.2 ng/mL；P<0.0001）。在PMX-DHP治疗期间，血清可溶性VE-钙黏蛋白水平的时间进程保持不变。在接受PMX-DHP治疗前，存活者与非存活者血清可溶性VE-钙黏蛋白水平无显著差异，并且在开始PMX-DHP治疗后的任何时间，两组之间该水平也无显著差异。可溶性VE-钙黏蛋白水平与临床数据之间无相关性，除了白细胞计数（r=-0.277，P=0.000９）。可溶性VE-钙黏蛋白水平与血管生成素1和2的水平之间无相关性。总之．无法证实脓毒症中VE-钙黏蛋白与毛细血管通透性之间的关系。可溶性VE-钙黏蛋白未反映在细胞间连接可塑性与完整性之间的平衡中，但通过其磷酸化或内化实现的VE-钙黏蛋白稳定可能与毛细血管通透性有关。
