Abstract: Arterial thrombosis is the underlying cause of a wide variety of cardiovascular diseases including myocardial infarction. All the currently used thrombolytic agents are plasminogen activators, which are very efficient in restoring the blood flow. They can convert plasminogen into plasmin and thus degrade fibrin. Despite the widespread use of established thrombolytic agents such as streptokinase, t-PA and u-PA, all these agents suffer from a number of inadequacies including resistance to reperfusion, occurrence of coronary reocclusion and bleeding complications. The quest continues for plasminogen activators with higher potency, specific thrombolytic activity, fibrin selectivity and longer half-life time. The recent progress in the protein engineering of plasminogen activators, including t-PA, u-PA, streptokinase, staphylokinase and other novel plasminogen activators, was presented in this article. We can conclude that the new generation of thrombolytic agents showed considerable potential with regard to improving the efficacy of thrombolytic therapy, and these progresses were based on the detailed understanding of the relationship between structure and function of thrombolytic agents. However, the risk of intracranial bleeding remains problematic and need more researches on the modification of thrombolytic agents.

Key words: thrombolytic agent, plasminogen activator, protein engineering, thrombolytic agent, plasminogen activator, protein engineering

摘要： 介绍了国内外溶栓剂蛋白质工程方面的新进展，主要涉及了组织型纤溶酶原激活剂(t-PA)、尿激酶型纤溶酶原激活剂(u-PA)、链激酶(SK)、葡萄球菌激酶(SAK)、DSPA及TSV-PA的研究进展。一些PA突变体及新型溶栓剂，如K2P、TNK-PA和STAR等的临床实验结果表明它们在延长体内半寿期、增强对血纤维蛋白选择性和溶栓效率等方面有较大的改进。但溶栓治疗造成的颅内出血等局部性出血问题仍是目前的难题之一，说明新型溶栓剂的研制有很大潜力。

关键词: 溶栓剂, 纤溶酶原激活剂, 蛋白质工程, 溶栓剂, 纤溶酶原激活剂, 蛋白质工程