尿激酶型纤溶酶原激活剂诱发的纤溶反应及其调节因子

目的 研究一些凝血和纤溶因子对尿激酶型纤溶酶原激活剂（uPA)诱发纤溶反应的调节作用及机制。方法 采用凝块溶解测定和纤维蛋白检测板测定观察了一些凝血和纤溶因子对uPA诱导的纤溶反应的影响及相互作用。结果 凝血酶激活的纤溶抑制因子（TAFI）对uPA或单链uPA（scuPA）诱发的纤溶反应具有明显的拮抗作用，凝血酶调节因子（TM）可明显增强其抑制作用，凝血酶对uPA诱导的纤溶反应没有明显的影响，但可抑制scuPA诱导的纤溶反应，该作用亦可被TM所增强或被水蛭素所消除。结论 凝血酶／TM可通过激活TAFI对uPA或scuPA诱导的纤溶反应产生抑制作用，凝血酶对scuPA诱发的纤溶反应的抑制作用亦可通过其对scuPA的裂解失活而实现。

Regulation of uPA-induced fibrinolysis

Objective To study the roles of fibrinolytic regulators in fibrinolysis induced by urokinase type plasminogen activator (uPA) and underlying mechanisms. Methods Clot lysis assay and fibrin detector plate were used for determining the effects of the regulators, including carboxypeptidase inhibitor (cPI), thrombin, thrombomodulin (TM) and hirudin, on the fibrinolysis induced by uPA or single chain uPA (scuPA). Results With clot lysis assay, uPA (2 nmol/L) or scuPA (6 nmol/L) gave no clot lysis in the absence of cPI, but they induced significant fibrinolysis in the presence of cPI (6 nmol/L), a specific inhibitor of thrombin activatable fibrinolysis inhibitor (TAFI), and again the uPA induced fibrinolysis was inhibited with the addition of TM (1 nmol/L or 10 nmol/L). Exogenous thrombin (3.8 nmol/L) did not influence uPA induced fibrinolysis, but it inhibited scuPA induced fibrinolysis. In fibrin detector plate, uPA and scuPA showed the same fibrinolytic activities in the absence of added thrombin and scuPA but not uPA was inactivated with the addition of thrombin (0.2 nmol/L), and the inactivation of scuPA was enhanced by TM (1 nmol/L), a stimulator of thrombin, or abolished by hirudin (285 nmol/L), a inhibitor of thrombin. Conclusion uPA or scuPA induced fibrinolysis is inhibited as a result of activation of TAFI by thrombin/TM and scuPA induced fibrinolysis may also be inhibited as a result of inactivation of scuPA via cleavage by thrombin.