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弥散性血管内凝血相关脓毒症中血管生成因子及其可溶性受体与器官功能障碍的关系的动态变化。

The dynamics of angiogenic factors and their soluble receptors in relation to organ dysfunction in disseminated intravascular coagulation associated with sepsis.

机构信息

Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo, 060-8638, Japan.

出版信息

Inflammation. 2013 Feb;36(1):186-96. doi: 10.1007/s10753-012-9534-6.

Abstract

We prospectively studied (1) the relationships between angiogenic factors, their soluble receptors and organ dysfunction and (2) the effects of disseminated intravascular coagulation (DIC)-induced platelet consumption, thrombin generation, and tissue hypoxia on the expression of the factors and receptors. Fifty patients with sepsis were classified into two subgroups: 37 patients with DIC and 13 patients without DIC. DIC patients showed higher Sequential Organ Failure Assessment (SOFA) scores, the prevalence of multiple organ dysfunction syndrome (MODS) and more increased soluble fibrin and lactate levels. We observed lower levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR2), angiopoietin 1 (Ang1) and Ang1/Ang2, and higher sVEGFR1 and Ang2 levels in DIC patients, but not significant differences in soluble Tie2 expression during the study period. The levels of VEGF, sVEGFR1, and Ang2 in DIC patients correlated with the SOFA scores. Clear differences were observed in the levels of Ang2 in the DIC patients between survivors and nonsurvivors and between those with and without MODS. The area under receiver operating characteristic curves for predicting death and MODS by Ang2 were 0.710 and 0.784, respectively. The VEGF levels showed a marked correlation with the platelet counts. Soluble fibrin and lactate levels independently predicted increases in the levels of VEGF, sVEGFR1, and Ang2 in DIC patients. In conclusion, VEGF, sVEGFR1, Ang2, and Ang1/Ang2, especially Ang2, may have roles in the development of MODS in sepsis associated with DIC, and VEGF, sVEGFR1, and Ang2 serum levels correlated with the extent of DIC-induced platelet consumption, thrombin generation, and blood lactate levels.

摘要

我们前瞻性地研究了(1)血管生成因子及其可溶性受体与器官功能障碍的关系,以及(2)弥散性血管内凝血(DIC)引起的血小板消耗、凝血酶生成和组织缺氧对这些因子和受体表达的影响。50 例脓毒症患者分为两组:37 例 DIC 患者和 13 例无 DIC 患者。DIC 患者的序贯器官衰竭评估(SOFA)评分较高,多器官功能障碍综合征(MODS)的发生率较高,可溶性纤维蛋白和乳酸水平升高。我们观察到 DIC 患者的血管内皮生长因子(VEGF)、可溶性 VEGF 受体 2(sVEGFR2)、血管生成素 1(Ang1)和 Ang1/Ang2 水平较低,sVEGFR1 和 Ang2 水平较高,但在研究期间可溶性 Tie2 表达没有显著差异。DIC 患者 VEGF、sVEGFR1 和 Ang2 水平与 SOFA 评分相关。DIC 患者 Ang2 水平在幸存者与非幸存者之间以及在有或无 MODS 患者之间存在明显差异。Ang2 预测死亡和 MODS 的受试者工作特征曲线下面积分别为 0.710 和 0.784。VEGF 水平与血小板计数呈显著相关。可溶性纤维蛋白和乳酸水平独立预测 DIC 患者 VEGF、sVEGFR1 和 Ang2 水平升高。总之,VEGF、sVEGFR1、Ang2 和 Ang1/Ang2,特别是 Ang2,可能在与 DIC 相关的脓毒症中 MODS 的发展中发挥作用,VEGF、sVEGFR1 和 Ang2 血清水平与 DIC 诱导的血小板消耗、凝血酶生成和血乳酸水平的程度相关。

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