Lijnen H R
Int J Clin Lab Res. 1996;26(1):1-6. doi: 10.1007/BF02644767.
Circumstantial evidence has been provided for a role of the human fibrinolytic or plasminogen/plasmin system in a variety of biological phenomena. Recently, generation of mice with single or combined deficiencies of main components of the fibrinolytic system, including plasminogen, tissue-type and urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and the cellular receptor for urokinase-type plasminogen activator has allowed the role of the fibrinolytic system in vivo to be established more conclusively. Plasminogen-deficient mice survive embryonic development, but develop spontaneous fibrin deposition due to an impaired thrombolytic potential, and suffer retarded growth and reduced fertility and survival. Plasminogen deficiency in man is extremely rare, but viable, although it is associated with thrombolic complications. Disruption of the plasminogen activator inhibitor-1 gene in mice induces a mild hyperfibrinolytic state and a greater resistance to venous thrombosis, but does not impair hemostasis. In contrast, in man, the inhibitor deficiency results in delayed rebleeding. Tissue-type plasminogen activator-deficient mice have a reduced thrombolytic potential, whereas mice deficient in the urokinase-type plasminogen activator occasionally develop spontaneous fibrin deposits in tissues and display deficient plasmin-mediated macrophage function. Mice deficient in both types of activator develop normally but are significantly less fertile, have retarded growth and shorter survival, and display a severe thrombotic phenotype in normal and inflamed tissues. At present, genetic deficiencies of either type activator have not been reported in man. The urokinase-type plasminogen activator/receptor system has been implicated in localized extracellular proteolytic activity. Receptor-deficient mice are, however, healthy, and fertile, and have a normal endogenous thrombolytic capacity; their macrophages have, however, an impaired (urokinase-type plasminogen activator mediated) plasminogen activating potential. Mice with single or combined inactivation of components of the plasminogen/plasmin system thus may be valuable models for studying physiological and pathophysiological processes in vivo.
已有间接证据表明人类纤维蛋白溶解或纤溶酶原/纤溶酶系统在多种生物学现象中发挥作用。最近，通过培育缺乏纤溶系统主要成分（包括纤溶酶原、组织型和尿激酶型纤溶酶原激活物、纤溶酶原激活物抑制剂 -1 以及尿激酶型纤溶酶原激活物的细胞受体）的单一或联合缺陷型小鼠，使得纤溶系统在体内的作用得以更确凿地确立。纤溶酶原缺陷型小鼠能够存活至胚胎发育完成，但由于溶栓潜能受损而出现自发性纤维蛋白沉积，并伴有生长发育迟缓、生育能力下降以及存活率降低的情况。人类纤溶酶原缺乏极为罕见，但即便存活也会伴有血栓形成并发症。小鼠体内纤溶酶原激活物抑制剂 -1 基因的破坏会引发轻度的高纤溶状态以及对静脉血栓形成更强的抵抗力，但不会损害止血功能。相比之下，在人类中，该抑制剂缺乏会导致出血延迟。组织型纤溶酶原激活物缺陷型小鼠的溶栓潜能降低，而尿激酶型纤溶酶原激活物缺陷型小鼠偶尔会在组织中出现自发性纤维蛋白沉积，并表现出纤溶酶介导的巨噬细胞功能缺陷。两种激活物都缺乏的小鼠发育正常，但生育能力显著降低，生长发育迟缓且存活时间缩短，并且在正常组织和炎症组织中均表现出严重的血栓形成表型。目前，尚未有关于人类任何一种激活物基因缺陷的报道。尿激酶型纤溶酶原激活物/受体系统与局部细胞外蛋白水解活性有关。然而，受体缺陷型小鼠健康且具有生育能力，并且具有正常的内源性溶栓能力；不过，它们的巨噬细胞（尿激酶型纤溶酶原激活物介导的）纤溶酶原激活潜能受损。因此，纤溶酶原/纤溶酶系统各成分单一或联合失活的小鼠可能是研究体内生理和病理生理过程的有价值模型。
