目的研究半合成β-1,4-葡聚糖硫酸钠(Na—MCS)的抗凝血效果和作用机制。方法采用凝固分析法、以肝素为阳性对照进行抗凝血效果的评价,再通过发色底物法对凝血因子进行抑制分析,揭示Na—MCS的抗凝血作用机制。结果0.6μg·mL^-1Na—MCS即可显著延长APTT和TT,但在更高浓度下对PT影响仍不大,使正常人血浆的APTT延长1倍的Na—MCS剂量为0.7μg·mL^-1,低于活性为150u·mg^-1的肝素。结论在一定浓度范围内,Na-MCS的抗凝血活性与肝素相当,Na—MCS通过抗凝血酶AT—Ⅲ的调节作用来抑制凝血因子IIa和Xa的活性,从而产生抗凝血作用。
Aim To investigate the anticoagulant efficacy and mechanism of a semi-synthesized sodium β-1,4-glucan sulfate (Na-MCS). Methods Anticoagulant activity was evaluated by means of coagulation assays in comparison with heparin. The anticoagulant mechanism of Na-MCS was disclosed by inhibitory analysis of the activities of coagulation factors using chromogenic substrates. Results 0. 6 μg·mL^-1 Na-MCS could significantly prolong APTT and TT, but has less effect on PT at an even higher concentration. The dosage of Na-MCS required to double APTT of normal human plasma was 0. 7 μg·mL^-1, lower than that of heparin with the activity of 150 u·mg^-1 Conclusion Na-MCS represented a potent anticoagulation activity in vitro, which matched the efficacy of heparin in a certain range of concentrations. Na-MCS exhibited anticoagulant activity due to inhibition of the coagulation factors IIa and Xa by the mediation of anti-thrombin AT-Ⅲ.