Ries Martin, Zenker Martin
Clinic for Paediatric and Adolescent Medicine, Memmingen, Germany.
Blood Coagul Fibrinolysis. 2003 Feb;14(2):203-9. doi: 10.1097/00001721-200302000-00014.
This study investigates, by slow binding kinetics methods, reaction kinetics of both plasmin types 1 and 2 with alpha -antiplasmin in the presence of increasing concentrations of either epsilon-amino-caproic acid (EACA) or soluble fibrin. All curves of plasmin-alpha -antiplasmin interaction followed the same pattern, indicating reversible slow binding inhibition with an initial loose complex and a following tight complex. Without soluble fibrin or EACA, differences between plasmin types 1 and 2 could be seen in the initial loose complex formation. The presence of increasing concentrations of EACA slowed down the first step of the reaction (without any effect on the second step), resulting in increasing values for K. Plasmin type 1 demonstrated a steep slope of K at an EACA concentration of 1 mmol/l. In plasmin type 2, the increase of K started at higher EACA concentrations. The value for K at a high EACA concentration (100 mmol/l) was the same for both plasmin types. In contrast to EACA, increasing concentrations of soluble fibrin slowed down both reaction steps. At high concentrations of soluble fibrin, the inhibitory effect of alpha -antiplasmin was almost completely abolished. Our data demonstrate that the effect of soluble fibrin and the lysine analogue EACA on plasmin-antiplasmin reactions are different and that the use of lysine analogues does not mimic fibrin in laboratory analyses of plasmin inhibition. In addition, our data indicate theoretical differences between plasmin type 1 and plasmin type 2, when used for local thrombolytic therapy.(2) (2) (i initial) (i initial) (i initial) (i initial) (2)
本研究采用慢结合动力学方法,在ε-氨基己酸(EACA)或可溶性纤维蛋白浓度不断增加的情况下,研究了1型和2型纤溶酶与α-抗纤溶酶的反应动力学。纤溶酶-α-抗纤溶酶相互作用的所有曲线都遵循相同的模式,表明存在可逆的慢结合抑制,最初形成松散复合物,随后形成紧密复合物。在没有可溶性纤维蛋白或EACA的情况下,1型和2型纤溶酶在最初松散复合物形成过程中存在差异。EACA浓度的增加减缓了反应的第一步(对第二步没有任何影响),导致K值增加。在EACA浓度为1 mmol/l时,1型纤溶酶的K值呈现陡峭斜率。在2型纤溶酶中,K值的增加始于更高的EACA浓度。在高EACA浓度(100 mmol/l)下,两种纤溶酶的K值相同。与EACA相反,可溶性纤维蛋白浓度的增加减缓了两个反应步骤。在高浓度可溶性纤维蛋白下,α-抗纤溶酶的抑制作用几乎完全消失。我们的数据表明,可溶性纤维蛋白和赖氨酸类似物EACA对纤溶酶-抗纤溶酶反应的影响不同,并且在纤溶酶抑制的实验室分析中,赖氨酸类似物的使用并不能模拟纤维蛋白。此外,我们的数据表明,在用于局部溶栓治疗时,1型纤溶酶和2型纤溶酶在理论上存在差异。