Kimata H, Koide T, Nakajima K, Kondo S
Tokyo Research Laboratories, Kowa Co., Ltd., Japan.
J Pharmacobiodyn. 1991 Jan;14(1):25-33. doi: 10.1248/bpb1978.14.25.
The localization of tissue plasminogen activator (t-PA) on microthrombi in various organs of disseminated intravascular coagulation rats (DIC rats) was investigated by using microautoradiographic technique. After the injection of [125I]fibrinogen, experimental DIC rats induced by the infusion of thrombin for 1 h were submitted to microautoradiograms (MARGMs) of some major organs. The radioactivity of [125I]fibrin thrombi, which were observed as silver grains, was localized in the glomeruli and parts of small vessels in the kidney. In the liver, microthrombi were seen in sinusoid vessels and on Kupffer cells. In addition, many microthrombi were noted in small vessels in the lung and marginal zones in the spleen. Two min after the intravenous administration of [125I]t-PA to DIC rats, many silver grains were observed on each MARGM of the kidney, lung, liver and spleen showing the formation of microthrombi. From the identical results with the observations of MARGMs after the injection of [125I]fibrinogen, we confirmed that t-PA was highly accumulated to microthrombi formed in small vessels of the organs. The scattered silver grains were widely observed on the hepatocytes. This result suggested that t-PA bound to the parenchymal cell surface might be transported into the hepatocytes by receptor-mediated endocytosis. On the other hand, when [125I]urokinase plasminogen activator [( 125I]u-PA) was administered intravenously to DIC rats, many silver grains were observed on MARGM of the proximal tubules in the kidney but not seen on MARGMs of the glomeruli in the kidney, nor in the lung, liver, and spleen. This observation suggested that u-PA might not have a characteristic to accumulate to thrombi.
采用显微放射自显影技术研究了组织型纤溶酶原激活剂（t-PA）在弥散性血管内凝血大鼠（DIC大鼠）各器官微血栓上的定位。注射[125I]纤维蛋白原后，对经凝血酶输注1小时诱导的实验性DIC大鼠的一些主要器官进行显微放射自显影（MARGMs）。作为银颗粒观察到的[125I]纤维蛋白血栓的放射性定位于肾脏的肾小球和部分小血管中。在肝脏中，微血栓见于窦状血管和库普弗细胞上。此外，在肺的小血管和脾脏的边缘区发现许多微血栓。给DIC大鼠静脉注射[125I]t-PA两分钟后，在肾脏、肺、肝脏和脾脏的每个MARGM上观察到许多银颗粒，表明形成了微血栓。根据注射[125I]纤维蛋白原后MARGMs的观察结果相同，我们证实t-PA高度聚集在器官小血管中形成的微血栓上。在肝细胞上广泛观察到散在的银颗粒。这一结果表明，结合到实质细胞表面的t-PA可能通过受体介导的内吞作用转运到肝细胞中。另一方面，当给DIC大鼠静脉注射[125I]尿激酶型纤溶酶原激活剂[（125I]u-PA）时，在肾脏近端小管的MARGM上观察到许多银颗粒，但在肾脏的肾小球、肺、肝脏和脾脏的MARGM上未观察到。这一观察结果表明，u-PA可能不具有聚集到血栓上的特性。
