Durand Eric, Helley Dominique, Al Haj Zen Ayman, Dujols Céline, Bruneval Patrick, Colliec-Jouault Sylvia, Fischer Anne-Marie, Lafont Antoine
Faculté de Médecine, Université Paris Descartes, Paris, France.
J Vasc Res. 2008;45(6):529-37. doi: 10.1159/000129687. Epub 2008 May 7.
Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model.
Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial apoptosis with staurosporine (10(-5)M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days.
The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue factor expression was significantly lower in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 +/- 28 vs. 102 +/- 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation.
LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH.
普通肝素和低分子量肝素(LMWHs)的治疗应用受到出血不良反应的限制。我们在一个实验模型中比较了低分子量岩藻聚糖(LMWF)和低分子量肝素的抗血栓形成作用。
用星形孢菌素(10⁻⁵M,30分钟)原位诱导雄性新西兰白兔股动脉内皮细胞凋亡,从而诱发血栓形成。从诱导凋亡前一天开始,动物每天接受两次皮下注射LMWF(15mg/kg)、LMWH(依诺肝素2.5mg/kg)或生理盐水(对照组),持续4天。
三组的凋亡程度和内皮剥脱程度相似。LMWF组的血栓形成评分显著低于LMWH组和对照组(p = 0.01)。LMWF组的组织因子表达显著低于对照组和LMWH组(p = 0.01)。注射LMWF后,组织因子途径抑制剂的血浆浓度显著升高(137±28对102±17;p = 0.01),而LMWH治疗后未观察到变化。LMWF没有延长出血时间或降低血小板聚集。
在这个实验模型中,LMWF在预防动脉血栓形成方面似乎比LMWH更有效。LMWF的出血风险也低于LMWH。