Fonseca Roberto J C, Oliveira Stephan-Nicollas M C G, Melo Fábio R, Pereira Maria G, Benevides Norma M B, Mourão Paulo A S
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
Thromb Haemost. 2008 Mar;99(3):539-45. doi: 10.1160/TH07-10-0603.
We compared sulfated galactans (SGs) from two species of red algae using specific coagulation assays and experimental models of thrombosis. These polysaccharides have an identical saccharide structure and the same size chain, but with slight differences in their sulfation patterns. As a consequence of these differences, the two SGs differ in their anticoagulant and venous antithrombotic activities. SG from G. crinale exhibits procoagulant and prothrombotic effects in low doses (up to 1.0 mg/kg body weight), but in high doses (>1.0 mg/kg) this polysaccharide inhibits both venous and arterial thrombosis in rats and prolongs ex-vivo recalcification time. In contrast, SG from B. occidentalis is a very potent anticoagulant and antithrombotic compound in low doses (up to 0.5 mg/kg body weight), inhibiting venous experimental thrombosis and prolonging ex-vivo recalcification time, but these effects are reverted in high doses. Only at high doses (>1.0 mg/kg) the SG from B. occidentalis inhibits arterial thrombosis. As with heparin, SG from G. crinale does not activate factor XII, while the polysaccharide from B. occidentalis activates factor XII in high concentrations, which could account for its procoagulant effect at high doses on rats. Both SGs do not modify bleeding time in rats. These results indicate that slight differences in the proportions and/or distribution of sulfated residues along the galactan chain may be critical for the interaction between proteases, inhibitors and activators of the coagulation system, resulting in a distinct pattern in anti- and procoagulant activities and in the antithrombotic action.
我们使用特定的凝血测定法和血栓形成实验模型，比较了两种红藻中的硫酸化半乳聚糖（SGs）。这些多糖具有相同的糖结构和相同大小的链，但硫酸化模式略有不同。由于这些差异，两种SGs在抗凝和静脉抗血栓形成活性方面有所不同。来自G. crinale的SG在低剂量（高达1.0 mg/kg体重）时表现出促凝血和促血栓形成作用，但在高剂量（>1.0 mg/kg）时，这种多糖可抑制大鼠的静脉和动脉血栓形成，并延长体外再钙化时间。相比之下，来自B. occidentalis的SG在低剂量（高达0.5 mg/kg体重）时是一种非常有效的抗凝和抗血栓形成化合物，可抑制静脉实验性血栓形成并延长体外再钙化时间，但在高剂量时这些作用会逆转。只有在高剂量（>1.0 mg/kg）时，来自B. occidentalis的SG才会抑制动脉血栓形成。与肝素一样，来自G. crinale的SG不会激活因子XII，而来自B. occidentalis的多糖在高浓度时会激活因子XII，这可能解释了其在高剂量时对大鼠的促凝血作用。两种SGs均不会改变大鼠的出血时间。这些结果表明，硫酸化残基在半乳聚糖链上的比例和/或分布的微小差异，可能对凝血系统的蛋白酶、抑制剂和激活剂之间的相互作用至关重要，从而导致抗凝和促凝活性以及抗血栓形成作用呈现出不同的模式。
