von der Möhlen M A, van Deventer S J, Levi M, van den Ende B, Wedel N I, Nelson B J, Friedmann N, ten Cate J W
Center of Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands.
Blood. 1995 Jun 15;85(12):3437-43.
A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.
一种重组内毒素中和蛋白rBPI23，已被证明在人类实验性内毒素血症中能部分预防内毒素诱导的纤溶和凝血系统激活。在一项安慰剂对照、双盲交叉研究中，8名志愿者接受两次静脉推注内毒素（40 EU/kg体重）的挑战，并同时接受rBPI23（1 mg/kg）或安慰剂（人血清白蛋白，0.2 mg/kg）。rBPI23治疗显著降低了内毒素诱导的纤溶反应，即减少了组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物、纤溶酶原激活物抑制剂抗原的释放，以及纤溶酶α2 -抗纤溶酶复合物的形成（每项P = 0.0078）。纤溶酶原激活物抑制剂活性也有所降低，但根据霍奇伯格方法差异不显著（P = 0.0304）。rBPI23输注减弱了内毒素诱导的促凝状态激活，表现为F1 + 2片段和TAT复合物增加（分别为P = 0.0391[根据霍奇伯格方法不显著]和0.0078）。这些结果表明，rBPI23能够在人类低剂量内毒素输注后降低纤溶和凝血系统的激活。
