Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis
Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis
复制标题
DOI：
10.1006/jsre.2002.6552
复制
发表时间：
2002-12-01
影响因子：
2.2
通讯作者：
Wakefield, T
中科院分区：
文献类型：
--
作者：
Myers, D;Farris, D;Wakefield, T
背景。本研究描述了小鼠静脉血栓形成的特征，并研究了粘附分子 P-选择素和 E-选择素以及抗炎细胞因子白细胞介素 10 (IL-10) 在血栓形成过程中发挥的重要作用。材料和方法。研究了自然历史方案（第 1 阶段）中的 C57BL/6（野生型）小鼠和后续方案（第 11 阶段）中 P-选择素、E-选择素、P/E-选择素和 IL-10 的基因靶向 (KO) 小鼠。通过在肾静脉正下方结扎产生下腔静脉血栓，处死小鼠并在长达12天后的不同时间点进行评估。结果。第一阶段：与假手术动物相比，在血栓形成后第 2 天发现中性粒细胞显着增加，在第 6 天发现单核细胞显着增加。发现静脉壁 P-选择素 mRNA（第 6 小时，第 2 天）显着增加，蛋白质增加（6 小时至第 6 天），而 E-选择素 mRNA 显着增加（第 2 天至第 6 天），E-选择素蛋白质增加较小。 IL-10 mRNA 随后（第 2 天至第 9 天）显着增加，且值逐渐增加。中性粒细胞与第 2 天的血栓形成之间存在正相关性 (r = 0.77)。H 期。与野生型凝血小鼠相比，E-选择素和 P/E-选择素双 KO 小鼠在第 2 天显示出最少的血栓，P < 0.01。此外，P/E-KO 小鼠在第 2 天表现出最低的炎症细胞外渗到静脉壁中。结论。这项研究证明了静脉壁中与静脉血栓形成相关的急性至慢性炎症反应。选择素的抑制减少了血栓形成。 (C) 2002 年爱思唯尔科学（美国）。
Background. This study characterizes venous thrombosis in the mouse and examines the important role that the adhesion molecules P-selectin and E-selectin and the anti-inflammatory cytokine interleukin-10 (IL-10) play in the thrombotic process.Materials and methods. C57BL/6 (wild-type) mice in a natural history protocol (Phase 1) and gene-targeted (KO) mice for P-selectin, E-selectin, P/E-selectin, and IL-10 in a follow-up protocol (Phase 11) were studied. Inferior vena caval thrombosis was produced by ligation just below the renal veins, and mice were sacrificed and evaluated at various time points up to 12 days later.Results. Phase I: A significant increase in neutrophils on day 2 and in monocytes on day 6 postthrombosis was found in ligated vs sham animals. An associated significant increase in vein wall P-selectin mRNA (6 h, day 2) and an increase in protein (6 h through day 6) were found, while E-selectin mRNA was significantly increased (day 2 through day 6), with a smaller increase in E-selectin protein. IL-10 mRNA increased significantly later (day 2 through day 9), with the values increasing progressively. A positive correlation existed (r = 0.77) between neutrophils and thrombosis at day 2. Phase H. The E-selectin and P/E-selectin double-KO mice showed the least thrombus at day 2 vs wild-type clotted mice, P < 0.01. Additionally, P/E-KO mice demonstrated the lowest inflammatory cell extravasation into the vein wall at day 2.Conclusions. This study demonstrates an acute to chronic inflammatory response in the vein wall associated with venous thrombosis. Inhibition of selectins decreased thrombus formation. (C) 2002 Elsevier Science (USA).