Cipriani Thales R, Gracher Ana Helena P, de Souza Lauro M, Fonseca Roberto J C, Belmiro Celso L R, Gorin Philip A J, Sassaki Guilherme L, Iacomini Marcello
Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR, Brazil.
Thromb Haemost. 2009 May;101(5):860-6.
Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.
对从柠檬酸果胶中获得的两种具有不同平均摩尔质量的化学硫酸化多糖的抗凝血和抗血栓形成活性以及出血效果进行了评估。低分子量（Pec-LWS，3600 g/mol）和高分子量硫酸化果胶（Pec-HWS，12000 g/mol）的结构基本相同，均由（1→4）连接的α-D-半乳糖醛酸链组成，其几乎所有的HO-2和HO-3基团都被硫酸取代。两种多糖在体外均具有抗凝血活性，尽管Pec-HWS在体内是一种更强效的抗血栓形成剂，在剂量为3.5 mg/kg体重时可完全抑制静脉血栓形成。令人惊讶的是，与肝素不同，Pec-HWS和Pec-LWS能够通过一种独立于抗凝血酶（AT）和/或肝素辅因子II（HCII）的机制直接抑制α-凝血酶和因子Xa。此外，在对静脉血栓形成具有100%有效性的剂量下，Pec-HWS的出血风险低于肝素，表明它是一种有前景的抗血栓形成剂。
