Kusada Akiko, Isogai Noritaka, Cooley Brian C
Medical College of Wisconsin, Department of Orthopaedic Surgery, Milwaukee, Wisconsin, USA.
Thromb Res. 2007;121(1):103-6. doi: 10.1016/j.thromres.2007.03.005. Epub 2007 Apr 25.
Murine models of arterial thrombosis have gained utility with applications in genetically manipulated mice. Implementation of current models requires specialized equipment and provides limited outcome measures. A new murine model of continuously monitored arterial thrombosis was created.
An electric injury was delivered to the exterior surface of the common carotid artery using the flat end of a 140-mum steel microsurgery needle connected to the anode of a 3-V battery source. Direct current was delivered for 30 s. The developing thrombus was apparent as a white, platelet-dominated region at the site of injury. This region was continuously monitored and recorded by videotape for 30 min. Subsequently, the thrombus area was measured directly on the TV monitor, generating a time course for thrombogenesis. In a further evaluation of the model, three pharmacologically treated groups of mice were evaluated, with drug infusion immediately before thrombus induction: (1) saline (control), (2) heparin (60 units/kg), and (3) GR144053, a GPIIb/IIIa-specific antagonist (10 mg/kg).
The basic model showed consistent thrombus development by 7-9 min, occasionally forming an occlusive thrombus. Most of the thrombi underwent one or more cycles of embolization and thrombus regrowth. In the experimental series, the heparin-treated group had a significantly decreased thrombus area versus controls (p<0.0001); the GR144053-treated mice had no apparent thrombus, supporting a dominant role of platelet aggregation in arterial thrombogenesis.
This new model is simple to do, uses readily available instrumentation, and provides a continuously recorded quantifiable measure of thrombogenesis.
动脉血栓形成的小鼠模型在基因工程小鼠中得到了广泛应用。当前模型的实施需要专门的设备,且提供的结果测量有限。创建了一种新的连续监测动脉血栓形成的小鼠模型。
使用连接到3伏电池阳极的140微米钢显微手术针的平端,对颈总动脉外表面施加电损伤。直流电施加30秒。正在形成的血栓在损伤部位表现为白色、以血小板为主的区域。该区域通过录像连续监测和记录30分钟。随后,直接在电视监视器上测量血栓面积,生成血栓形成的时间进程。在对该模型的进一步评估中,对三个药物治疗组的小鼠进行了评估,在诱导血栓形成前立即进行药物输注:(1)生理盐水(对照组),(2)肝素(60单位/千克),(3)GR144053,一种GPIIb/IIIa特异性拮抗剂(10毫克/千克)。
基础模型显示在7至9分钟时血栓形成一致,偶尔形成闭塞性血栓。大多数血栓经历了一个或多个栓塞和血栓再生长周期。在实验系列中,肝素治疗组的血栓面积与对照组相比显著减小(p<0.0001);GR144053治疗的小鼠没有明显的血栓,支持血小板聚集在动脉血栓形成中起主导作用。
这种新模型操作简单,使用现成的仪器,并提供血栓形成的连续记录的可量化测量。