Aisina R B, Moukhametova L I, Varfolomeyev S D
Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119992, Russia.
Biochemistry (Mosc). 2003 Nov;68(11):1252-60. doi: 10.1023/b:biry.0000009141.17272.6c.
Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro at 37 degrees C under the influence of recombinant staphylokinase, single-chain urokinase-type plasminogen activator (scu-PA), and their simultaneous and consecutive combinations. Staphylokinase and scu-PA caused concentration- and time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA separately caused 50% lysis in 4 h. At these equally effective concentrations staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen than scu-PA. Combinations of staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action on the clots. The synergy of thrombolytic action was more pronounced on the simultaneous addition of the two agents than on their consecutive addition, scu-PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM) or scu-PA (15 nM) induced 24% and 2% lysis, respectively, whereas the simultaneous and consecutive combination of the same concentrations of these agents induced 58% and 50% lysis, respectively. The simultaneous combination of 15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in the thrombolytic effect as compared to the expected total effect of the individual agents. Synergic combinations of the two agents caused lesser exhaustion of plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen as compared with the expected total effect of these agents used separately. Thus, simultaneous and consecutive combinations of staphylokinase and scu-PA in a relatively narrow range of their concentrations possessed synergistic fibrin-selective thrombolytic action on the plasma clot in vitro.
在37摄氏度下，于体外研究了重组葡萄球菌激酶、单链尿激酶型纤溶酶原激活剂（scu-PA）及其同时和先后组合对浸于血浆中的人血浆凝块的溶解动力学。葡萄球菌激酶和scu-PA引起凝块的浓度和时间依赖性溶解；32 nM葡萄球菌激酶和75 nM scu-PA分别在4小时内引起50%的溶解。在这些等效有效浓度下，4小时内葡萄球菌激酶诱导的血浆纤溶酶原、α2-抗纤溶酶和纤维蛋白原的消耗明显少于scu-PA。葡萄球菌激酶（<30 nM）和scu-PA（<75 nM）的组合对凝块具有协同溶栓作用。两种药物同时添加时的溶栓协同作用比先后添加（葡萄球菌激酶30分钟后添加scu-PA）更明显。添加后4小时，25 nM葡萄球菌激酶或15 nM scu-PA分别诱导24%和2%的溶解，而相同浓度的这两种药物同时和先后组合分别诱导58%和50%的溶解。与预期的各药物单独作用的总效应相比，15 nM葡萄球菌激酶和15 nM scu-PA的同时组合导致溶栓效果最大增加3.8倍。与这些药物单独使用的预期总效应相比，两种药物的协同组合导致血浆纤溶酶原、α2-抗纤溶酶和纤维蛋白原的消耗更少。因此，在相对较窄的浓度范围内，葡萄球菌激酶和scu-PA的同时和先后组合在体外对血浆凝块具有协同的纤维蛋白选择性溶栓作用。
