Gailani David, Cheng Qiufang, Ivanov Ivan S
Division of Hematology/Oncology, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Ave., Nashville, TN, 37232, USA,
Methods Mol Biol. 2015;1229:483-96. doi: 10.1007/978-1-4939-1714-3_37.
Evaluating anticoagulants in animal thrombosis models is a standard component of preclinical drug testing. Mice are frequently used for these initial evaluations because a variety of thrombosis models have been developed and are well characterized in this species, and the animals are relatively inexpensive to maintain. Because mice have a natural resistance to forming intravascular thrombi, vessel injury is required to induce intravascular clot formation. Several methods have been established for inducing arterial or venous thrombosis in mice. For the purpose of testing heparin-based drugs, we adapted a well-established model in which thrombus formation in the carotid artery is induced by exposing the vessel to ferric chloride. For studying anticoagulant effects on venous thrombosis, we use a model in which the inferior vena cava is ligated and the size of the resulting clots is measured. The most common adverse effect of anticoagulation therapy is bleeding. The effect of heparin-based anticoagulants can be tested in mice in a simple tail bleeding assay.
在动物血栓形成模型中评估抗凝剂是临床前药物测试的标准组成部分。小鼠经常用于这些初步评估，因为已经开发了多种血栓形成模型，并且在该物种中具有良好的特征，而且饲养这些动物相对便宜。由于小鼠对形成血管内血栓具有天然抵抗力，因此需要血管损伤来诱导血管内血栓形成。已经建立了几种在小鼠中诱导动脉或静脉血栓形成的方法。为了测试基于肝素的药物，我们采用了一种成熟的模型，即通过将血管暴露于氯化铁来诱导颈动脉血栓形成。为了研究抗凝剂对静脉血栓形成的影响，我们使用一种模型，即结扎下腔静脉并测量由此产生的血栓大小。抗凝治疗最常见的不良反应是出血。基于肝素的抗凝剂的效果可以在小鼠中通过简单的尾部出血试验进行测试。
