Matsuno H, Uematsu T, Nagashima S, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
J Pharmacol Methods. 1991 Jul;25(4):303-17. doi: 10.1016/0160-5402(91)90030-9.
We report a new and reproducible model of thrombosis in the rat femoral artery. The thrombosis is initiated by endothelial injury subsequent to photochemical reaction between systemically injected rose bengal (10 mg/kg, i.v.) and transillumination of filtered xenon lamp (wave length: 540 nm) from the outside of the vessel. The blood flow of the femoral artery, which was monitored by a pulsed doppler flow meter, was fully stopped in 348.68 +/- 36.18 sec (n = 12) after i.v. injection of rose bengal under irradiation with green light. The formation of massive thrombosis was readily evident by visual inspection. The processes of primary endothelial injury and the subsequent formation of thrombosis during this manipulation were observed by light microscopy and analysed by the scanning and transmission electron microscopy. Pretreatment with heparin (30, 100 or 300 units/kg, i.v.) 10 min before rose bengal injection dose-dependently prolonged the time required to interrupt the blood flow. The thrombolytic activity of a tissue-type plasminogen activator (tPA) was also investigated. After the establishment of stable thrombotic occlusion of the femoral artery, infusion of tPA was started from the contralateral femoral vein for 30 min at the rate of 30 or 100 micrograms/kg/min. The occluded artery was reperfused in 2 out of 10 rats and in 9 out of 12 at the lower and higher rates of tPA infusion, respectively. That heparin could prevent the arterial occlusion and that tPA could reperfuse the occluded artery are observations consistent with the histopathological ones that the primary lesion of endothelium injured photochemically activates the platelet aggregation to form platelet-rich thrombus with extensions of erythrocyte-rich lesions. This model is expected to be a useful tool for evaluating the antithrombotic and thrombolytic agents.
我们报告了一种新型的、可重复的大鼠股动脉血栓形成模型。血栓形成起始于全身注射孟加拉玫瑰红（10 mg/kg，静脉注射）与从血管外部用滤过的氙灯（波长：540 nm）进行透照之间的光化学反应导致的内皮损伤。通过脉冲多普勒流量计监测，在静脉注射孟加拉玫瑰红并在绿光照射下，股动脉血流在348.68±36.18秒（n = 12）内完全停止。通过肉眼检查很容易观察到大量血栓的形成。在此操作过程中，通过光学显微镜观察原发性内皮损伤及随后血栓形成的过程，并通过扫描电子显微镜和透射电子显微镜进行分析。在注射孟加拉玫瑰红前10分钟用肝素（30、100或300单位/kg，静脉注射）预处理，可剂量依赖性地延长中断血流所需的时间。还研究了组织型纤溶酶原激活剂（tPA）的溶栓活性。在股动脉形成稳定的血栓闭塞后，从对侧股静脉以30或100微克/千克/分钟的速率开始输注tPA 30分钟。分别以较低和较高的tPA输注速率，在10只大鼠中有2只、12只中有9只闭塞动脉实现了再灌注。肝素可预防动脉闭塞以及tPA可使闭塞动脉再灌注，这些观察结果与组织病理学观察结果一致，即光化学损伤的内皮原发性病变激活血小板聚集，形成富含血小板的血栓，并伴有富含红细胞的病变扩展。该模型有望成为评估抗血栓和溶栓药物的有用工具。
