Kimata H, Nakajima K, Yamamoto S, Hasegawa A
Tokyo Research Laboratories, Kowa Co., Ltd., Japan.
J Pharmacobiodyn. 1990 Dec;13(12):745-50. doi: 10.1248/bpb1978.13.745.
The binding affinity; incorporation and adsorption, of human tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) for blood clots was investigated in vitro. In order to study the incorporation, the blood clot formation was performed after mixing [125I]t-PA or [125I]u-PA with the blood obtained from human and several animal species. The radioactivities of [125I]t-PA incorporated in blood clots of human, dog, rat and rabbit were higher than those of [125I]u-PA. The adsorption study was carried out by immersing the blood clot in saline containing the [125I]plasminogen activators (PAs). The adsorptions of [125I]t-PA to blood clots of human and animals were higher than those of [125I]u-PA. The results suggest that t-PA has a much higher affinity for fibrin in blood clots than u-PA. The blood clot lysis caused by the clot-bound PAs was investigated using the [125I]fibrin-containing blood clots pretreated with t-PA or u-PA. In the human blood clot, the clot-bound t-PA showed a dose-dependent clot lysis at the concentrations of t-PA ranging from 0.3 to 3 nM, while the clot-bound u-PA has little clot-lytic activity. The t-PA bound to the human blood clot showed the most effective clot lysis as compared with those bound to the animal blood clots.
在体外研究了人组织型纤溶酶原激活剂（t-PA）和尿激酶型纤溶酶原激活剂（u-PA）对血凝块的结合亲和力、掺入及吸附情况。为研究掺入情况，在将[125I]t-PA或[125I]u-PA与人及几种动物的血液混合后进行血凝块形成实验。掺入人、狗、大鼠和兔子血凝块中的[125I]t-PA的放射性高于[125I]u-PA。吸附研究是通过将血凝块浸入含有[125I]纤溶酶原激活剂（PAs）的盐溶液中进行的。[125I]t-PA对人及动物血凝块的吸附高于[125I]u-PA。结果表明，t-PA对血凝块中纤维蛋白的亲和力远高于u-PA。使用经t-PA或u-PA预处理的含[125I]纤维蛋白的血凝块研究了血凝块结合型PAs引起的血凝块溶解情况。在人血凝块中，血凝块结合型t-PA在t-PA浓度为0.3至3 nM时呈现剂量依赖性的血凝块溶解，而血凝块结合型u-PA几乎没有血凝块溶解活性。与人血凝块结合的t-PA与动物血凝块结合的t-PA相比，显示出最有效的血凝块溶解作用。
