Vinazzer H, Stemberger A, Haas S, Blümel G
Thromb Res. 1982 Aug 1;27(3):341-52. doi: 10.1016/0049-3848(82)90081-0.
The influence of different heparin fractions and of a synthetic polysulfated polysaccharide (SP54) on the fibrinolytic mechanism was examined. In vitro, a significant shortening of the euglobulin lysis time (ELT) was found after addition of standard mucosa heparin, of high MW heparin and of SP 54 respectively. Low MW heparin fractions had no influence on the ELT. Simultaneously with the shortening of the ELT an activation of factor XII and of kallikrein was observed. A similar effect was found in groups of volunteers after i.v. or s.c. injections and even after oral administration of SP 54. The effect of venous occlusion on the ELT and on the activation of factor XII was considerably increased when heparin or SP 54 was injected 2 h prior to the test. When a comparable concentration of the test substances was added to plasma samples before and after venous occlusion, the effect on the ELT was much less pronounced than after injection whilst the effect on factor XII was comparable in both tests. From these results the conclusion was drawn that activation of fibrinolysis by polysulfated polysaccharides is achieved by an endogenous pathway as well as by an increased availability of the vascular activator. The magnitude of the activation of fibrinolysis partly depends on the MW of the substance but apparently also on the degree of sulfation since a low MW substance with a high number of sulfate bonds such as SP 54 was considerably more active than the low MW fraction of standard heparin.
研究了不同肝素组分以及一种合成多硫酸化多糖(SP54)对纤溶机制的影响。在体外,分别加入标准黏膜肝素、高分子量肝素和 SP54 后,发现优球蛋白溶解时间(ELT)显著缩短。低分子量肝素组分对 ELT 无影响。在 ELT 缩短的同时,观察到因子 XII 和激肽释放酶的激活。静脉内或皮下注射甚至口服 SP54 后,在志愿者组中也发现了类似的效果。当在试验前 2 小时注射肝素或 SP54 时,静脉闭塞对 ELT 和因子 XII 激活的影响显著增加。当在静脉闭塞前后向血浆样本中加入相当浓度的受试物质时,对 ELT 的影响远不如注射后明显,而对因子 XII 的影响在两种试验中相当。从这些结果得出结论,多硫酸化多糖对纤溶的激活是通过内源性途径以及通过增加血管激活剂的可用性来实现的。纤溶激活的程度部分取决于物质的分子量,但显然也取决于硫酸化程度,因为具有大量硫酸键的低分子量物质如 SP54 比标准肝素的低分子量组分活性高得多。