Antithrombotic activity of a fucosylated chondroitin sulphate from echinoderm: sulphated fucose branches on the polysaccharide account for its antithrombotic action
Antithrombotic activity of a fucosylated chondroitin sulphate from echinoderm: sulphated fucose branches on the polysaccharide account for its antithrombotic action
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DOI：
10.1046/j.1365-2141.1998.00769.x
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发表时间：
1998-06-01
影响因子：
6.5
通讯作者：
Gray, E
中科院分区：
文献类型：
--
作者：
Mourao, PAS;Guimaraes, MAM;Gray, E
从海参体壁中提取的岩藻糖基化硫酸软骨素样多糖和相同多糖的化学修饰衍生物的抗血栓形成活性已经使用家兔的停滞血栓形成模型进行了评估。静脉内施用天然多糖以剂量依赖性方式减少血栓形成，并且在1.5 mg/kg（60 IU/kg）体重的剂量下，在10分钟停滞后完全防止血栓形成。在静脉注射抗血栓剂量的放射性标记的多糖后，观察到从血浆中除去放射性和离体APTT值降低之间的相关性，证明抗血栓形成的有效性取决于循环多糖的水平，而不是取决于多糖对血管的间接作用，多糖中葡糖醛酸羧基的减少不影响其体外和体内活性。多糖的部分去岩藻糖基化和脱水作用都消除了其所有的抗凝或抗血栓作用。
The antithrombotic activity of a fucosylated, chondroitin-sulphate-like polysaccharide extracted from the body wall of sea cucumber, and of chemically modified derivatives of the same polysaccharide, have been assessed using a stasis thrombosis model in rabbits. Intravenous administration of the native polysaccharide reduced thrombosis in a dose-dependent manner and, at a dose of 1.5 mg/kg (60 IU/kg) body weight, completely prevented thrombosis after 10min stasis. Removal of the sulphated fucose branches of the polysaccharide abolished antithrombotic effectiveness.After intravenous injection of an antithrombotic dose of radioactively labelled polysaccharide, a correlation was observed between removal of radioactivity from the plasma and decrease in ex vivo APTT values, demonstrating that antithrombotic effectiveness depends on the level of circulating polysaccharide rather than on an indirect effect of the polysaccharide on the vascular endothelium.Reduction of the glucuronic acid carboxyl groups in the polysaccharide did not affect its in vitro and in vivo activities. Both partial defucosylation and desulphation of the polysaccharide abolished all its anticoagulant or antithrombotic action.