锌对纤维蛋白凝块形成的促凝血作用。

The procoagulant effect of zinc on fibrin clot formation.

作者信息

Marx G, Eldor A

出版信息

Am J Hematol. 1985 Jun;19(2):151-9. doi: 10.1002/ajh.2830190207.

DOI:10.1002/ajh.2830190207

Abstract

The influence of Zn+2 on fibrin clot formation was investigated by measuring its effect on the clotting times of fibrinogen exposed to thrombin. It was observed with either human or bovine thrombin that 0.01-0.1 mM Zn+2 induced significant reductions of clotting times in a concentration-dependent manner. The procoagulant effect of Zn+2 occurred in the presence of Ca+2 but was inhibited by metal chelating agents. Higher levels of Zn+2 (greater than 0.2 mM final concentration) were required to accelerate thrombin-induced clot formation in the presence of citrate or oxalate. Similarly with oxalated human plasma, greater than 0.2 mM Zn+2 decreased the clotting time. Cations such as Mg+2 and Mn+2 caused little change in clotting times. As an extension of these findings, we examined the effect of Zn+2 on the inhibition of thrombin by antithrombin-III (AT-III). The presence of as little as 0.006 mM Zn+2 in an incubating mixture of thrombin and AT-III severely reduced the inhibitory activity of AT-III towards thrombin. It was observed that the relative intrinsic fluorescence emission of human thrombin decreased upon exposure to Zn+2 but was unaffected by Mg+2 or Mn+2. It is suggested that Zn+2 can form a complex with thrombin, which results in altered reactivity towards fibrinogen and decreased inhibition by AT-III.

摘要

通过测量锌离子（Zn²⁺）对暴露于凝血酶的纤维蛋白原凝血时间的影响，研究了Zn²⁺对纤维蛋白凝块形成的影响。使用人凝血酶或牛凝血酶均观察到，0.01 - 0.1 mM的Zn²⁺以浓度依赖的方式显著缩短了凝血时间。Zn²⁺的促凝作用在钙离子（Ca²⁺）存在时出现，但被金属螯合剂抑制。在柠檬酸盐或草酸盐存在的情况下，需要更高水平的Zn²⁺（终浓度大于0.2 mM）来加速凝血酶诱导的凝块形成。同样，对于草酸盐处理的人血浆，大于0.2 mM的Zn²⁺可缩短凝血时间。镁离子（Mg²⁺）和锰离子（Mn²⁺）等阳离子对凝血时间几乎没有影响。作为这些发现的延伸，我们研究了Zn²⁺对抗凝血酶III（AT - III）抑制凝血酶的影响。在凝血酶和AT - III的孵育混合物中，仅0.006 mM的Zn²⁺就严重降低了AT - III对凝血酶的抑制活性。观察到，人凝血酶暴露于Zn²⁺后其相对固有荧光发射降低，但不受Mg²⁺或Mn²⁺影响。提示Zn²⁺可与凝血酶形成复合物，这导致其对纤维蛋白原的反应性改变以及被AT - III抑制的能力降低。