Antithrombotic and Anticoagulant Activities of a Low Molecular Weight Fucoidan by the Subcutaneous Route
Antithrombotic and Anticoagulant Activities of a Low Molecular Weight Fucoidan by the Subcutaneous Route
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DOI：
10.1055/s-0037-1614484
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发表时间：
1999-03
影响因子：
6.7
通讯作者：
J. Millet;S. C. Jouault;S. Mauray;J. Theveniaux;C. Sternberg;C. B. Vidal;Anne-Marie Fischer
中科院分区：
文献类型：
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作者：
J. Millet;S. C. Jouault;S. Mauray;J. Theveniaux;C. Sternberg;C. B. Vidal;Anne-Marie Fischer
岩藻聚糖（从棕色海藻中提取的高分子量硫酸多糖）具有抗凝血和抗血栓形成作用。根据其化学结构和来源，它们通过催化丝氨酸蛋白酶抑制剂（抗凝血酶和肝素辅因子II）来抑制凝血酶。在这项研究中，低分子量（LMW）岩藻聚糖硫酸酯的8 kDa的高分子量馏分的化学降解得到的。这种新化合物的抗血栓形成和抗凝活性进行了比较，低分子量肝素（LMWH），达肝素，皮下给药后的兔子。这种低分子量岩藻依聚糖具有剂量相关的静脉抗血栓活性，单次皮下注射后2小时，ED 80约为20 mg/kg。其活性与达肝素相当（接近200抗Xa IU/kg），单次皮下注射后30分钟达到最大。注射后1 ~ 4 h活性保持稳定（约70%），但到8h消失。与达肝素相反，抗血栓活性与凝血酶凝固时间（TCT）延长或抗Xa活性增加无关。两种化合物均出现APTT轻微延长。这种静脉抗血栓活性与体外凝血酶生成减少和凝血酶生成试验中滞后期显著增加相关。因此，与达肝素相比，LMW岩藻依聚糖具有强效抗血栓形成活性和潜在较弱的出血作用（即对凝血试验的影响较小，出血时间延长较小）。
Summary Fucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.