摘要
目的研究水蛭素对尿激酶诱导的纤溶作用的影响,并分析可能的机制。方法采用尿激酶为纤溶激酶,复钙柠檬酸钠抗凝血浆为纤溶酶原来源的体外溶栓模型,通过测定纤溶产物D-D imm er生成量,微孔板分光光度法跟踪纤溶过程,比较水蛭素与肝素对纤溶的影响。运用土豆羧肽酶抑制剂(CPI)对TAFIa的专一性抑制作用,分析水蛭素与肝素对TAFI活化的影响。结果水蛭素组D-D imm er较肝素组高(P<0.01),水蛭素加CPI组较水蛭素组更高(P<0.01);微孔板分光光度法跟踪纤溶过程,肝素组有明显的纤溶停止和血栓再形成倾向,水蛭素组则可观察到明显的溶栓现象,水蛭素加CPI组效果最好。结论对尿激酶诱导的纤溶,水蛭素比肝素有更好的间接促纤溶作用,其原因主要是水蛭素能有效抑制再次血凝的发生,减少了尿激酶和纤溶酶原的短暂性耗竭。在这一过程中,水蛭素不能彻底抑制TAFI活化,表明对TAFI活化的抑制可能不是水蛭素促尿激酶纤溶作用的主要原因。
Aim To investigate the effect of hirudin on clotlysis induced by uPA and its possible mechanism. Methods The in vitro clotolysis model consisted of pre-prepared blood clot, uPA as plasminogen activator, recalcified plasma as in plasminogen source, and hirudin or heparin as anticoagulant. The clotolysis was detected with microplate spectrophotometer and analyzing D-Dimmer; the product of clotlysis, with D-Dimmer ELISA Kit. Carboxypeptidase inhibitor from potato （CPI） , a special inhibitor of TAFIa, was used to test effect of heparin and hirudin on activation of TAFI. Results The level of D-Dimmer in plasma containing hirudin was higher than that in plasma containing heparin after 2 hour clotlysis （P 〈 0. 01 ） , but lower than that in plasma containing hirudin plus CPI （P 〈 0. 01 ）. With microplate spectrophotometer, clot generation in the heparin group, but stimulation of clotlysis in the hirudin groups, was observed. A stronger stimulation the effect was observed in the group of hirudin plus CPI. Conclusions Hirudin has a stronger stimulation effect than heparin does on the clotolysis induced by uPA through inhibiting clot generation and reducing the temporary exhaustion of uPA and plasminogen. The result that hirudin could not inhibit TAFI activationcompletely indicates that the inhibition of TAFI activation is not a main reason for the enhancement of uPA-induced clotlysis by hirudin.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第1期89-93,共5页
Chinese Pharmacological Bulletin
基金
江苏省自然科学基金资助项目(NoBK2001165)
关键词
水蛭素
尿激酶
纤溶
hirudin
clotolysis
carboxypeptidase inhibitor from potato（CPI）
uPA
