Hagimori Masayori, Kamiya Seitaro, Yamaguchi Yasuchika, Arakawa Masayuki
Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7, Huis Ten Bosch, Sasebo 859-3298, Japan.
Pharmacol Res. 2009 Oct;60(4):320-3. doi: 10.1016/j.phrs.2009.04.010. Epub 2009 Apr 24.
The carrageenan-induced tail thrombosis model in rats and mouse is useful for evaluating compounds having antithrombotic effects in drug discovery projects as an in vivo model. However, the frequency of thrombosis is low, and the signs of thrombosis are not constant under the standard conditions. In this study, we modified this model on the basis of hypercoagulability, endothelial injury, and alteration in the normal blood flow. The simple ligation to alter blood flow in rats significantly improved the frequency and signs of thrombosis after intravenous kappa-carrageenan injection. In particular, 1mg/kg kappa-carrageenan injection in combination with 10 min ligation at the tail increased the frequency of thrombosis to almost 100% in rats. These results suggest that this modified model has great advantages over the previously used conditions for evaluating the effects of antithrombotic and thrombolytic agents.
角叉菜胶诱导的大鼠和小鼠尾部血栓形成模型,作为一种体内模型,在药物研发项目中对于评估具有抗血栓作用的化合物很有用。然而,血栓形成的频率较低,并且在标准条件下血栓形成的迹象并不稳定。在本研究中,我们基于高凝状态、内皮损伤和正常血流改变对该模型进行了改良。在大鼠中简单结扎以改变血流,显著提高了静脉注射κ-角叉菜胶后血栓形成的频率和迹象。特别是,在大鼠中注射1mg/kg κ-角叉菜胶并结合尾部10分钟结扎,使血栓形成频率几乎增加到100%。这些结果表明,这种改良模型在评估抗血栓和溶栓药物的作用方面比以前使用的条件具有很大优势。