低分子量肝素抗凝机制的研究

Study of anticoagulant mechanism of low molecular weight heparin.

作者信息

Hamano S, Nishiyama M, Komatsu H, Miyata H, Ikeda S, Sakuragawa N

机构信息

Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., Hotaka, Japan.

出版信息

Thromb Res. 1992 Mar 15;65(6):801-8. doi: 10.1016/0049-3848(92)90118-t.

DOI:10.1016/0049-3848(92)90118-t

PMID:1321995

Abstract

The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and AT III was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and AT III with stronger affinity to AT III than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and AT III with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, AT III did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between AT III and FR-860, but not that between AT III and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, AT III and thrombin.

摘要

使用FR - 860 - 琼脂糖凝胶和普通肝素（UF - 肝素）琼脂糖凝胶研究了低分子量肝素（FR - 860）和普通肝素与因子Xa（F.Xa）、凝血酶及抗凝血酶III（AT III）的结合能力。FR - 860不能直接与F.Xa结合。FR - 860与凝血酶和AT III结合，对AT III的亲和力强于对凝血酶的亲和力。另一方面，UF - 肝素与F.Xa、凝血酶和AT III结合，对AT III的亲和力最强，其次是凝血酶和F.Xa。AT III介导F.Xa与FR - 860之间的结合，并加速F.Xa与UF - 肝素之间的反应。另一方面，AT III不影响凝血酶与FR - 860或UF - 肝素之间的结合。二异丙基氟磷酸处理的凝血酶抑制AT III与FR - 860之间的结合，但不抑制AT III与UF - 肝素之间的结合。这些结果表明，FR - 860的抗F.Xa活性由AT III介导。此外，FR - 860和UF - 肝素之间抗凝血酶活性的差异取决于形成FR - 860或UF - 肝素、AT III和凝血酶三元复合物的能力。