【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.更多还原

【Abstract】 We have generated recombinant human K₂tPA. 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 K₂tPA administered i.v. to dogs at doses of 1×10⁶　IU/kg, 5×10⁶　IU/kg and 2.5×10⁶　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 K₂tPA inhibited the aggregation activity of platelet.更多还原