重组人组织型纤溶酶原激活剂缺失变体的药效学研究  

A Pharmalogical Study on Recombinant Human K_2tPA

作　　者：赵专友[1] 刘厚孝[1] 张菁[2] 陈于红[2] 张巍[2] 朱镇华[2] 王石泉[2] 刘建宁[2] 

机构地区：[1]天津药物研究院药理室,天津300193 [2]南京大学分子医学研究所,南京210093

出　　处：《南京大学学报（自然科学版）》2004年第1期16-27,共12页Journal of Nanjing University（Natural Science）

基　　金：国家重大科技专项"创新药物和中药现代化"(2002AA2Z3451)

摘　　要：　犬静脉给予重组人组织型纤溶酶原激活剂缺失变体(K2tPA)1×106IU/kg、5×105IU/kg、2.5×105IU/kg对冠脉血栓产生显著的溶栓效果,栓塞冠脉血管很快出现再通,高、中、低剂量组残存血栓较溶剂对照组分别减少了72.7%、55.6%、42.5%;心肌梗死范围明显缩小.血纤维蛋白原明显降解,凝血酶原时间、凝血酶时间及陶土激活部分凝血酶时间明显延长,但抗凝血酶活性无显著改变.伤口出血量增加,出血时间延长.以上指标与等剂量(5×105IU/kg)的德国BoehringerMannheimGmbH产品Retavase作用相似.离体家兔血小板凝集实验结果表明:重组人K2tPA对家兔血小板聚集功能具有明显的抑制作用.We have generated recombinant human K_2tPA. The engineered strain shown in this study was very stable. The purity of the resulting protein was higher than 95%, and its specific activity was over 500　000　IU/mg. In the current study, recombinant K_2tPA administered i.v. to dogs at doses of 1×10~6　IU/kg, 5×10~6　IU/kg and 2.5×10~6　IU/kg produced obvious effects of coronary thrombolysis, and the coronary artery demonstrated that reperfusion occurred rapidly. The residual thrombi decreased to 72.7%, 55.6% and 42.5% respectively as compared with the control. The areas of myocardial infarction decreased apparently. Fibrinogen degraded significantly. Prothrombin time, thrombin time and activated partial thromplastin time were prolonged significantly, but there was no significant influence on the anti thrombin activity. The wound bleeding amount increased and the bleeding time was prolonged. In vitro experiment showed that K_2tPA inhibited the aggregation activity of platelet.

关 键 词：重组人组织型纤溶酶原激活剂 缺失变体 药效学 溶栓 纤维蛋白原 血小板聚集 心脑血管病 

分 类 号：R54[医药卫生—心血管疾病] Q5[医药卫生—内科学]