Anti-C5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis
Anti-C5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis
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DOI：
10.1016/s0002-9440(10)61133-9
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发表时间：
2002-05-01
影响因子：
6
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Laudes, IJ;Chu, JC;Ward, PA
脓毒症和创伤是引起弥散性血管内凝血和多器官功能障碍综合征的两个最常见的原因。弥散性血管内凝血和全身炎症反应综合征常导致多器官功能障碍综合征。本研究探讨了大鼠盲肠结扎穿孔（CLP）脓毒症模型中过敏毒素C5 a与凝血/纤溶系统变化之间的关系。与用免疫前IgG处理的大鼠（31%）相比，用抗C5 a处理的CLP动物的存活率（63%）大大提高。在CLP大鼠治疗免疫前IgG有明显增加促凝血活性的活化部分凝血活酶时间和凝血酶原时间的延长，血小板计数减少，血浆纤维蛋白原水平增加。凝血酶形成的证据表明，早期消费的因子VII：C，随后消费的因子XI：C和IX：C和抗凝血酶和凝血酶-抗凝血酶复合物和D-二聚体的水平增加。纤溶酶原血浆水平降低，组织纤溶酶原激活物和纤溶酶原激活物抑制剂水平升高，表明纤溶激活有限。这些参数中的大多数在用抗C5 a处理的CLP大鼠中逆转。脓毒症期间C5 a的产生可能直接或间接导致止血缺陷，其可通过阻断C5 a来减少。
Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.