Kitazato K, Kitazato K T, Nagase H, Minamiguchi K
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Thromb Res. 1996 Oct 15;84(2):111-20. doi: 10.1016/0049-3848(96)00166-1.
We characterized the antithrombotic, haemorrhagic, and ex vivo anticoagulant effects of a recently identified depolymerized holothurian glycosaminoglycan (DHG), and compared these effects with those of unfractionated heparin (UFH), low molecular weight heparin (LMWH), and dermatan sulfate (DS). In thrombin-induced venous thrombus formation in rats, DHG had a significant preventive effect at 0.3 mg/kg or more at 5 min after i.v., administration. UFH, LMWH, and DS also showed a significant antithrombotic effect at 0.3, 0.3, and 1 mg/kg, respectively, under the same experimental conditions. After rat tail transection, DHG, UFH, LMWH, and DS prolonged the bleeding time significantly at 10, 1, 1, and 10 mg/kg, respectively, at 5 min after i.v., injection. Therefore, DHG exerts its antithrombotic effect with less bleeding than UFH and LMWH in experimental animals. DHG prolonged the activated partial thromboplastin time in a dose-dependent manner at 0.3-3 mg/kg, at which dose an antithrombotic effect was exhibited without any significant haemorrhagic effect. All of these glycosaminoglycans prolonged thrombin clotting time markedly at their haemorrhagic doses.
我们对最近鉴定出的一种海参解聚糖胺聚糖（DHG）的抗血栓形成、出血和体外抗凝作用进行了表征，并将这些作用与普通肝素（UFH）、低分子量肝素（LMWH）和硫酸皮肤素（DS）的作用进行了比较。在大鼠凝血酶诱导的静脉血栓形成实验中，静脉注射后5分钟，DHG在0.3mg/kg及以上剂量时具有显著的预防作用。在相同实验条件下，UFH、LMWH和DS分别在0.3、0.3和1mg/kg剂量时也显示出显著的抗血栓形成作用。大鼠尾部横断后，静脉注射后5分钟，DHG、UFH、LMWH和DS分别在10、1、1和10mg/kg剂量时显著延长出血时间。因此，在实验动物中，DHG发挥抗血栓形成作用时的出血情况比UFH和LMWH少。DHG在0.3 - 3mg/kg剂量下以剂量依赖方式延长活化部分凝血活酶时间，在该剂量下表现出抗血栓形成作用且无任何显著出血作用。所有这些糖胺聚糖在其出血剂量下均显著延长凝血酶凝血时间。
