不同分子量硫酸皮肤素的抗血栓活性

Antithrombotic effects of different molecular weight dermatan sulfate

目的 研究不同相对分子质量硫酸皮肤素(DS)的抗血栓活性。方法 采用美国药典的羊血浆法测定不同相对分子质量的DS的抗凝血活性,电刺激大鼠动脉血栓形成法测定其体内抗血栓活性,以及生色底物法测定其激活肝素辅因子Ⅱ(HCⅡ)抗凝血酶活性。结果 相对分子质量分别为27.5×103,8.0×103,5.3×103和4.0×103的DS和低分子硫酸皮肤素(LMWDS1,LMWDS2和LMWDS3)的抗凝效价分别为4.00,2.25,0.94和0.54 u·mg-1;体内抗血栓活性的血栓堵塞时间(OT)值分别为58.12,50.58,123.90和133.53 min,均较生理盐水组19.79 min显著延长;体外激活HCⅡ抗凝血酶活性分别为223.23,123.71,89.29和58.00 u·mg-1。结论 随着LMWDS相对分子质量的降低,其抗凝血活性降低,体外激活HCⅡ抗凝血酶活性也降低,但体内抗血栓活性增强。

OBJECTIVE: To study the antithrombotic effects of different molecular weight dermatan sulfate (DS). METHODS: The anticoagulant activity of DS and low molecular weight dermatan sulfates (LMWDSs) in vitro were measured with USP method. The antithrombotic effects of them in vivo were studied using the method of stimulating thrombosis with electricity in rat artery, and their anti-factor II a activities mediated by activating heparin cofactor II (HCII) in vitro were determined by the UV method with chromogenic substrate. RESULTS: The anticoagulant activities of DS and LMWDSs with molecular weight of 27.5, 8.0, 5.3 and 4.0 × 103 were 4.00, 2.25, 0.94 and 0.54 u&middotmg-1 respectively. The antithrombotic effects of DS and LMWDSs expressed by occlusion times in vivo were 58.12, 50.58, 123.90 and 133.53 min respectively, all of which were significantly higher than that of NS group (19.79 min). Their anti-factor II a activities mediated by activating HCII were 223.23, 123.71, 89.29 and 58.00 u&middotmg-1 respectively. CONCLUSION: With the decrease of molecular weight, the anticoagulant activities and the anti-factor II a activities mediated by activating heparin cofactor II of DS decreased, but the antithrombotic effects increased.