Matsuno H, Uematsu T, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Br J Pharmacol. 1993 Dec;110(4):1278-9. doi: 10.1111/j.1476-5381.1993.tb13954.x.
The thrombolytic effects of the plasminogen/plasminogen activator chimera (SUN9216), comprising the fibrin-binding kringle 1 domain of plasminogen and two kringle and the serine protease domain of the wild-type tissue plasminogen activator (t-PA) including a modification of the mannose glycosylation on the kringle 1 of t-PA (PK1 delta FE1X), was compared with tht of t-PA by use of a photochemically induced thrombus (PIT) in the rat femoral artery. When SUN9216 was administered either as an i.v. infusion (1.0 mg kg-1) or as a single bolus i.v. injection (1.0 mg kg-1), all parameters were markedly improved compared to t-PA administered as an i.v. infusion (3.0 mg kg-1). A higher concentration of plasminogen activator (PA) activity in plasma was observed after administration of SUN9216 which persisted for longer than that after t-PA. It is concluded that the thrombolytic effect of SUN9216 is markedly greater than that of t-PA.
将包含纤溶酶原的纤维蛋白结合kringle 1结构域、两个kringle以及野生型组织纤溶酶原激活剂（t-PA）的丝氨酸蛋白酶结构域（包括对t-PA的kringle 1上的甘露糖糖基化进行修饰，即PK1 delta FE1X）的纤溶酶原/纤溶酶原激活剂嵌合体（SUN9216）的溶栓作用，与t-PA的溶栓作用在大鼠股动脉光化学诱导血栓（PIT）模型中进行了比较。当以静脉输注（1.0 mg kg-1）或单次静脉推注（1.0 mg kg-1）方式给予SUN9216时，与以静脉输注（3.0 mg kg-1）方式给予t-PA相比，所有参数均有显著改善。给予SUN9216后，血浆中纤溶酶原激活剂（PA）活性浓度更高，且持续时间比给予t-PA后更长。得出结论，SUN9216的溶栓作用明显强于t-PA。
