研究TAFIa作为抗血栓药物靶的意义

The Possibility of TAFIa as A Target of Anti-thrombosis

目的论证TAFIa作为溶栓与抗栓治疗药物靶的可能性。方法通过TAFIa专一性抑制剂存在条件下,低浓度t-PA诱导的纤溶试验以及内纤溶试验,研究抑制TAFIa对纤溶的促进作用。结果通过体外水蛭素抗凝的小剂量t-PA纤溶试验证明,即使在抗凝剂水蛭素存在时,抑制TAFIa活性仍可促进纤溶产物-D-Dimer的生成,并且在一定的t-PA浓度范围内,与t-PA浓度呈正相关。通过跟踪加入TAFIa专一性抑制剂CPI的t-PA诱导的内纤溶过程,发现在低剂量t-PA内纤溶试验中,抑制TAFIa活性可以明显缩短纤溶时间。结论通过抑制TAFIa的活性,可促进t-PA诱导的纤溶,并且可以促进微血栓的降解,抑制某些情况下的微血栓形成,这提示了TAFI可作为微血栓预防和治疗靶的可能。

Objective To investigate the possibility of TAFIa as the target of thrombolysis and antithrombosis. Methods The anti-thrombesis effect of TAFIa inhibition was tested by tPA-induced clotlysis tests and internal clotlysis with the TAFIa special inhibitor existing. Results The in vitro tPA-induced clotlysis tests with hirudin showed that TAFIa inhibition can obviously increase the formation of fibrinolysis end product D-dimer even hirudin coexisting, and there was a positive correlation between the thrombelysis enhancement effect and tPA dose. In the tPA-induced internal clotlysis tests with the TAFIa special inhibitor CPI, TAFIa inhibition can overfly shorten the fibrinolysis time. Conclusion TAFIa inhibition can obviously enhance the fibrinolysis, indicating a new possible approach for thrombolysis especially anti-thrombosis.