Martin U, Sponer G, Strein K
Department of Pharmacology, Boehringer Mannheim GmbH, Germany.
Blood Coagul Fibrinolysis. 1993 Apr;4(2):235-42. doi: 10.1097/00001721-199304000-00004.
The effects of the unglycosylated recombinant plasminogen activator BM 06.022, consisting of the kringle 2 and protease domains of tissue-type plasminogen activator (t-PA), on clot lysis were evaluated in an in vitro system. Fresh and aged 125I-labelled human platelet-poor (PPP) and platelet-rich plasma (PRP) and whole blood clots were immersed in human plasma. Clot lysis was quantitated by measurement of released 125I. Fresh PPP clots were time- and concentration-dependently lysed by BM 06.022, alteplase, melanoma t-PA (mt-PA), and urokinase. Fifty per cent clot lysis at 4 h required 3.2-, 6.4- and 15.2-fold higher nM concentrations of mt-PA, BM 06.022, and urokinase respectively compared with alteplase. Maximal lysis (Emax) at 4 h was similar (84.1-87.6%) for BM 06.022, alteplase, and mt-PA, but lower (65.3 +/- 0.6%) for urokinase. Emax for BM 06.022 was lower (P < 0.05) than for alteplase for fresh and aged PRP and whole blood clot lysis. These data suggest that in vitro BM 06.022 achieved, compared with alteplase, the same maximal efficacy in fresh PPP-clot lysis despite a lower potency, but was less effective in lysing aged and fresh PRP and whole blood clots.
由组织型纤溶酶原激活剂（t-PA）的kringle 2和蛋白酶结构域组成的未糖基化重组纤溶酶原激活剂BM 06.022对凝块溶解的作用在体外系统中进行了评估。将新鲜和陈旧的125I标记的人贫血小板血浆（PPP）、富血小板血浆（PRP）和全血凝块浸入人血浆中。通过测量释放的125I对凝块溶解进行定量。新鲜PPP凝块被BM 06.022、阿替普酶、黑色素瘤t-PA（mt-PA）和尿激酶进行时间和浓度依赖性溶解。与阿替普酶相比，在4小时时50%的凝块溶解分别需要浓度高3.2倍、6.4倍和15.2倍的nM浓度的mt-PA、BM 06.022和尿激酶。BM 06.022、阿替普酶和mt-PA在4小时时的最大溶解率（Emax）相似（84.1 - 87.6%），但尿激酶的较低（65.3±0.6%）。对于新鲜和陈旧的PRP以及全血凝块溶解，BM 06.022的Emax低于阿替普酶（P < 0.05）。这些数据表明，在体外，与阿替普酶相比，BM 06.022在新鲜PPP凝块溶解中虽效力较低但能达到相同的最大疗效，但在溶解陈旧和新鲜的PRP以及全血凝块方面效果较差。
