Kimata H, Nakajima K, Koide T, Yamamoto S, Kondo S
Tokyo Research Laboratories Kowa Co., Ltd., Japan.
J Pharmacobiodyn. 1990 Dec;13(12):751-9. doi: 10.1248/bpb1978.13.751.
The localization of tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) on thrombi was investigated in disseminated intravascular coagulation rats (DIC rats) induced by thrombin. One hour after the intravenous infusion of thrombin to rats, the plasma fibrinogen level decreased, while the plasminogen activator activity in the plasma euglobulin fraction increased. The whole body autoradiography was studied after an injection of [125I]fibrinogen in DIC rats. The high radioactivity which indicated the presence of microthrombi was observed in the renal cortex, liver, spleen and lung. Furthermore, a large venous thrombus with higher radioactivity was observed in the abdominal vena cava. These results show that the thrombin-treated animal is one of the best DIC models. After the intravenous administration of [125I]t-PA, the autoradiograms of DIC rats showed a radioactivity in the blood and much higher radioactivities in the renal cortex, spleen and lung in comparison with the normal rat. However, there was no difference in the distribution of [125I]u-PA between normal and DIC rats at all. The strong radioactivity of [125I]t-PA but not [125I]u-PA was observed on the surface of large thrombus in the vena cava. These results suggest that t-PA localizes more preferentially on microthrombi than u-PA. The ratio of the radioactivity in the tissue to that in the blood was calculated to compare quantitatively the localization of [125I]t-PA and [125I]u-PA on microthrombi formed in organs.(ABSTRACT TRUNCATED AT 250 WORDS)
在由凝血酶诱导的弥散性血管内凝血大鼠（DIC大鼠）中，研究了组织型纤溶酶原激活剂（t-PA）或尿激酶型纤溶酶原激活剂（u-PA）在血栓上的定位。给大鼠静脉输注凝血酶1小时后，血浆纤维蛋白原水平下降，而血浆优球蛋白组分中的纤溶酶原激活剂活性增加。在DIC大鼠注射[125I]纤维蛋白原后进行全身放射自显影研究。在肾皮质、肝脏、脾脏和肺中观察到表明存在微血栓的高放射性。此外，在腹静脉中观察到一个放射性更高的大静脉血栓。这些结果表明，经凝血酶处理的动物是最佳的DIC模型之一。静脉注射[125I]t-PA后，DIC大鼠的放射自显影片显示血液中有放射性，与正常大鼠相比，肾皮质、脾脏和肺中的放射性要高得多。然而，正常大鼠和DIC大鼠之间[125I]u-PA的分布完全没有差异。在腔静脉的大血栓表面观察到[125I]t-PA有强烈放射性，而[125I]u-PA没有。这些结果表明，与u-PA相比，t-PA更优先定位于微血栓上。计算组织与血液中放射性的比值，以定量比较[125I]t-PA和[125I]u-PA在器官中形成的微血栓上的定位。（摘要截短于250字）
