Krishnamurti C, Bolan C, Colleton C A, Reilly T M, Alving B M
Department of Hematology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Blood. 1993 Dec 15;82(12):3631-6.
The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.
纤溶酶原激活物抑制剂-1（PAI-1）活性升高导致的纤溶缺陷在促进体内纤维蛋白沉积中的作用尚未完全明确。本研究比较了凝血酶或安克洛酶（一种可使纤维蛋白原凝固的蛇毒衍生酶）在PAI-1水平升高的兔体内诱导纤维蛋白形成的效果。一组雄性新西兰兔静脉注射内毒素以增加内源性PAI-1活性，随后输注1小时的安克洛酶或凝血酶；另一组正常兔在输注安克洛酶或凝血酶期间静脉注射人重组PAI-1（rPAI-1）。输注结束30分钟后，通过组织病理学评估肾脏纤维蛋白沉积情况。单独接受内毒素、rPAI-1、安克洛酶或凝血酶的动物未形成肾血栓。所有接受内毒素治疗的兔在输注安克洛酶（n = 4）或凝血酶（n = 6）时均出现纤维蛋白沉积。接受rPAI-1和安克洛酶的7只兔中有7只出现纤维蛋白沉积，而接受rPAI-1和凝血酶的6只兔中只有1只出现（P <.01）。在体外，凝血酶可被正常兔血浆、纯化的抗凝血酶III或血栓调节蛋白灭活，而安克洛酶则不会。数据表明，PAI-1水平升高可促进输注安克洛酶的兔体内纤维蛋白沉积，但对输注凝血酶的兔则无此作用。在内毒素治疗的兔中，凝血酶输注时出现的纤维蛋白沉积可能是由于促凝活性抑制降低所致，而非PAI-1活性增加。
