Flight Simone M, Masci Paul P, Lavin Martin F, Gaffney Patrick J
School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Blood Coagul Fibrinolysis. 2006 Jul;17(5):417-20. doi: 10.1097/01.mbc.0000233374.79593.57.
In-vitro experimentation was performed on porcine and human blood to determine their comparative responsiveness to a novel fibrinolytic inhibitor and thereby assess whether the pig is a suitable animal model for subsequent in-vivo testing of this inhibitor. Thromboelastography showed the clots formed from porcine whole blood to be highly resistant to tissue plasminogen activator (t-PA)-catalyzed lysis, and this communication offers the resistance of porcine plasminogen to activation by t-PA as an explanation. Porcine blood containing 100 and 1500 IU/ml added t-PA lysed very slowly, having LY30 values of 1.9 +/- 1.4 and 2.9 +/- 1.9%, respectively. In contrast, the LY30 values for the human clots containing 100 and 1500 IU/ml t-PA were 77.1 +/- 6.3 and 93.3 +/- 1.3%, respectively. Moreover, purified porcine plasminogen was activated very slowly by added t-PA in the presence of both human and porcine fibrin. Activation of plasminogen by the endogenous activators, as measured by the euglobulin clot lysis time, was greatly prolonged for the pig (22 +/- 3 h) compared with the human (3.5 +/- 1.5 h). These results suggest caution in using the pig as an experimental model when studying the effects of various agents on fibrinolysis.
在猪和人血液上进行了体外实验，以确定它们对一种新型纤溶抑制剂的相对反应性，从而评估猪是否是该抑制剂后续体内测试的合适动物模型。血栓弹力图显示，猪全血形成的凝块对组织纤溶酶原激活剂（t-PA）催化的溶解具有高度抗性，本报告提出猪纤溶酶原对t-PA激活的抗性作为解释。添加100和1500 IU/ml t-PA的猪血液溶解非常缓慢，LY30值分别为1.9±1.4%和2.9±1.9%。相比之下，含有100和1500 IU/ml t-PA的人凝块的LY30值分别为77.1±6.3%和93.3±1.3%。此外，在人和猪纤维蛋白存在的情况下，添加的t-PA对纯化的猪纤溶酶原的激活非常缓慢。通过优球蛋白凝块溶解时间测量，猪的内源性激活剂对纤溶酶原的激活与人类（3.5±1.5小时）相比大大延长（22±3小时）。这些结果表明，在研究各种药物对纤溶的影响时，使用猪作为实验模型时应谨慎。
