溶栓剂蛋白质工程的新进展  

Recent Progresses in the Protein Engineering of Thrombolytic Agents

作　　者：张彦斌[1] 徐长法[1] 

机构地区：[1]北京大学蛋白质工程及植物基因工程国家重点实验室,北京100871

出　　处：《北京大学学报（自然科学版）》2000年第2期286-294,共9页Acta Scientiarum Naturalium Universitatis Pekinensis

基　　金：国家863 计划资助项目!(8631032102)

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。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.

关 键 词：溶栓剂 纤溶酶原激活剂 蛋白质工程 T-PA U-PA 

分 类 号：R94[医药卫生—药剂学]