Farias W R, Nazareth R A, Mourão P A
Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Thromb Haemost. 2001 Dec;86(6):1540-6.
Sulfated D-galactans occur on the red algae Botryocladia occidentalis as three fractions that differ in their sulfate content. Fractions F2 and F3 are potent anticoagulants. Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. The inhibition potency increases simultaneously with the sulfate content of the fractions. The antithrombotic activity of these sulfated D-galactans was investigated on an experimental thrombosis model in which thrombus formation was induced by a combination of stasis and hypercoagulability. In contrast with heparin. the sulfated D-galactans showed a dual dose-response curve preventing thrombosis at doses up to approximately 0.5 mg/ kg body weight but losing the effect at higher doses. This unexpected behavior is probably due to a combined action of the sulfated D-galactan as anticoagulant and also as a strong inducer of platelet aggregation. In platelet-depleted animals the antithrombotic activity at higher dose of sulfated D-galactan is restored and almost total inhibition of thrombus formation is achieved. The sulfated D-galactan has no hemorrhagic effect even at high doses, possibly as a consequence of its effect on platelet aggregation. At comparable dose heparin has an intense bleeding effect. These results indicate that new polysaccharides, with well-defined structures, can help to distinguish events, such as antithrombotic and anticoagulant activities, bleeding and platelet-aggregating effects, which are obscure when induced simultaneously by a single compound.
硫酸化D-半乳聚糖以三种硫酸含量不同的组分形式存在于红藻西方葡萄藻中。组分F2和F3是强效抗凝剂。与肝素一样，它们通过抗凝血酶和/或肝素辅因子II增强对凝血酶和Xa因子的抑制作用。抑制效力随组分的硫酸含量同时增加。在由血流淤滞和高凝状态联合诱导血栓形成的实验性血栓形成模型上研究了这些硫酸化D-半乳聚糖的抗血栓活性。与肝素不同，硫酸化D-半乳聚糖呈现双剂量反应曲线，在剂量高达约0.5mg/kg体重时可预防血栓形成，但在更高剂量时失去该作用。这种意外行为可能是由于硫酸化D-半乳聚糖作为抗凝剂以及作为血小板聚集的强诱导剂的联合作用。在血小板减少的动物中，硫酸化D-半乳聚糖较高剂量时的抗血栓活性得以恢复，并且几乎完全抑制血栓形成。硫酸化D-半乳聚糖即使在高剂量时也没有出血作用，这可能是其对血小板聚集作用的结果。在相当剂量下，肝素具有强烈的出血作用。这些结果表明，具有明确结构的新多糖有助于区分诸如抗血栓和抗凝活性、出血和血小板聚集作用等事件，这些事件在由单一化合物同时诱导时是模糊不清的。
