Development of new fibrinolytic agents.
Development of new fibrinolytic agents.
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DOI：
10.2174/138161206776056065
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发表时间：
2006-02
影响因子：
3.1
通讯作者：
S. Ueshima;O. Matsuo
中科院分区：
文献类型：
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作者：
S. Ueshima;O. Matsuo
由于凝血系统和血小板的激活触发血栓形成，具有抗凝或抗血小板功能的药物被用于抗血栓处理作用。然而，在生理状态下，纤溶系统起到抗血栓的作用，将血栓从循环中清除。纤维蛋白是血栓形成的主要成分，纤溶系统对纤维蛋白的溶解起着重要作用。因此，凝血和纤溶系统之间的平衡调节血栓的形成。目前，激活纤溶系统的新型药物已在临床上应用于溶栓治疗。纤溶系统的主要因子是纤溶酶，它由纤溶酶原激活剂（PA）从纤溶酶原中激活。纤溶酶原激活剂主要用于溶栓治疗。PA有两种类型。一种是非纤维蛋白特异性PA，如链激酶（SK）和双链尿激酶型PA （tcu-PA，尿激酶），另一种是纤维蛋白特异性PA，如组织型PA （t-PA）和单链尿激酶型PA （scuu -PA）。近年来，一些t-PA衍生物已被开发出来，获得了比天然t-PA更长的半衰期，并允许单丸给药。此外，还开发了新的纤维蛋白特异性PA，如葡萄激酶和蝙蝠PA。人们已经做了许多尝试来开发能够诱导内皮细胞释放t-PA的药物。本文就新型纤溶药物的研究进展作一综述。
Since the activation of coagulation system and platelets triggers the thrombosis, the agents possessing anticoagulation or anti-platelet function have been used for the antithrombotic procession actions. However, in the physiological condition, the fibrinolytic system serves as antithrombotic, which removes the thrombus from the circulation. The fibrinolytic system plays an important role in the dissolution of fibrin, which is the main component of thrombus. So that, the balance between the coagulation and fibrinolytic system regulates the formation of thrombus. Now, the new agents that activate the fibrinolytic system have been clinically applied for the thrombolytic therapy. The main factor in fibrinolytic system is the plasmin, which is activated from the plasminogen by the plasminogen activator (PA). The plasminogen activator is mainly used for the thrombolytic therapy. There are two types of PA. One is the non fibrin-specific PA such as streptokinase (SK) and two-chain urokinase-type PA (tcu-PA, urokinase), and another is the fibrin-specific PA such as tissue-type PA (t-PA) and single-chain urokinase-type PA (scu-PA). Recently, some derivatives of t-PA have been developed to obtain the longer half-life than native t-PA and allowed to administrate as the single-bolus. Further, the new fibrin-specific PA such as staphylokinase and bat-PA has been developed. Many attempts have been made to develop the agents that would induce the release of t-PA from endothelial cells. In this review, the development of new fibrinolytic agents is summarized.