Wiedermann Ch J, Römisch J
Division of General Internal Medicine, Department of Internal Medicine, University of Innsbruck.
Acta Med Austriaca. 2002;29(3):89-92. doi: 10.1046/j.1563-2571.2002.02012.x.
Leukocyte-endothelial cell interaction and microvascular perfusion failure are characteristic deteriorations of the microcirculation in endotoxaemia and are known to play a crucial role in the development of septic multiple organ dysfunction. Recent studies have indicated that antithrombin III treatment is capable of significantly ameliorating these microcirculatory disorders. Endothelial cells have important anticoagulant systems, including the heparan sulfate-antithrombin system. Antithrombin III stimulates prostacyclin generation in endothelial cells by interacting with heparan sulfate of endothelial cells and inhibits cytokine and tissue factor production in endothelial cells and monocytes. Similar mechanisms may be involved in cellular actions of antithrombin III causing desensitization of chemoattractant receptors of leukocytes by activating the heparan sulfate proteoglycan, syndecan-4. Thus, antithrombin III might be among the useful agents for treating coagulation abnormalities associated with sepsis or other inflammation because it inhibits not only coagulation but also downregulation of anticoagulant activities of endothelial cells and affects leukocyte activation.
白细胞与内皮细胞相互作用以及微血管灌注衰竭是内毒素血症中微循环的典型恶化表现，并且已知在脓毒症多器官功能障碍的发展中起关键作用。最近的研究表明，抗凝血酶III治疗能够显著改善这些微循环障碍。内皮细胞具有重要的抗凝系统，包括硫酸乙酰肝素-抗凝血酶系统。抗凝血酶III通过与内皮细胞的硫酸乙酰肝素相互作用刺激内皮细胞生成前列环素，并抑制内皮细胞和单核细胞中的细胞因子和组织因子产生。抗凝血酶III的细胞作用可能涉及类似机制，即通过激活硫酸乙酰肝素蛋白聚糖syndecan-4导致白细胞趋化因子受体脱敏。因此，抗凝血酶III可能是治疗与脓毒症或其他炎症相关的凝血异常的有用药物之一，因为它不仅抑制凝血，还能抑制内皮细胞抗凝活性的下调并影响白细胞激活。
