中分子质量岩藻聚糖硫酸酯的抗血栓活性及作用机制

Antithrombotic activities and its mechanisms of fucoidan with middle molecular weight

目的观察中分子质量岩藻聚糖硫酸酯(MMWF)的抗血栓作用并探讨其作用机制。方法 50只大鼠随机分为正常对照组、模型组、阿司匹林组、MMWF0.25 mg·kg^(-1)组和0.1mg·kg^(-1)组,采用下腔静脉血栓模型,考察血栓湿重和血栓抑制率。酶联免疫吸附测试法(ELISA)测定动物血浆抗凝血酶-Ⅲ(AT-Ⅲ)、蛋白质C(PC)、纤溶酶原(PLG)、组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)指标。另外50只大鼠按前述分组,通过大鼠血瘀模型考察血液流变学改变。结果在静脉血栓模型中,与正常对照组比较,模型组的AT-Ⅲ和PC活性、t-PA含量及t-PA/PAI-1比值均显著降低,PAI-1和PLG含量显著增加(均P<0.01)。与模型组和阿司匹林组比较,MMWF 0.25 mg·kg^(-1)组和0.1 mg·kg^(-1)组血栓湿重均显著减轻(均P<0.01),AT-Ⅲ和PC无显著改变(P>0.05),t-PA含量和t-PA/PAI-1比值显著升高,PAI-1和PLG含量显著降低(均P<0.01)。在血瘀模型中,与正常对照组比较,模型组的全血黏度、血浆黏度、血细胞比容、红细胞沉降率及红细胞沉降率方程K值等血液流变学指标均有明显升高(均P<0.01)。与模型组比较,MMWF 0.25 mg·kg^(-1)和0.1 mg·kg^(-1)组上述指标均显著改善(P<0.05或P<0.01)。结论 MMWF具有明显的抗血栓作用,其机制可能与增加纤溶作用和改善血液流变学性质有关。

AIM To investigate the antithrombotic activity of fucoidan with middle molecular weight （MMWF） and possible mechanisms. METHODS Fifty rats were randomly divided into 5 groups, including normal control group, model group, aspirin group and MMWF groups （0.25 mg-kg-1 and 0.1 mg-kg-1）. The inferior caval venous thrombosis model was used to examine the antithrombotic activity of MMWF. The activity of antithrombin 3 （AT-IU）, protein C （PC）, plasminogen （PLG）, tissue plasminogen activator （t-PA） and plasminogen activator inhibitor-1 （PAI-1） in plasma were determined by ELISA to evaluate the effects of the drugs on the inhibitory activity on anticoagulants and fibrinolytic system. Furthermore, hemorheologic indices were observed in other fifty rats with stagnation of blood. RESULTS In rats with inferior caval venous thrombosis model, compared with the normal control group, the activities of AT-m and PC of the model group were significantly decreased （P 〈 0.01）, the content of t-PA was decreased, the contents of PAI-1 and PLG were increased, and the ratio of t-PA/PAI-1 was decreased （P 〈 0.01 for all）. Thrombus wet weight of MMWF 0.25 mg-kg-1 and MMWF 0.1 mg-kg-1 group were significantly decreased （P 〈 0.01 for both）, the content of t- PA was increased, the activitys of PAI-1 and PLG were decreased, and the ratio of t-PA/PAI-1 was increased （P 〈 0.01 for all） , but there were no significantly difference of the content of AT-Ⅲ and PC （P 〉 0.05 for both） in comparison with the model group and the aspirin group. In rats with the blood stasis model, all the parameters of hemorheology of the model group were significantly increased when compared with the normal control group （P 〈 0.01 for all）. The parameters of hemorheology were significantly improved with MMWF 0.25 mg-kg-1 and MMWF 0.1 mg·kg^-1 administration （P 〈 0.05 or P 〈 0.01）. CONCLUSION MMWF could inhibit venous thrombosis by improving fibronolysis and hemorrheology.