三种栓塞模型建立及对P2Y12ADP受体拮抗剂适应性评价Efficacy of P2Y12ADP Receptor Antagonists in Three Animal Thrombosis Model
孔焕育,程小荣,刘锐锋
KONG Kuanyu,LI Bolan,LIU Ruifeng
摘要(Abstract):
目的通过普拉格雷对三种动物栓塞模型的作用,探讨所建立的几种栓塞模型是否适用于P2Y12ADP受体拮抗剂药效学评价。方法 120只小鼠随机分成普拉格雷治疗组和阴性对照组,灌胃给药3 d,末次给药后2 h,尾静脉注射胶原和肾上腺素混合物,计算存活率;216只SD大鼠随机分成普拉格雷治疗组和阴性对照组。灌胃给药3 d,末次给药后2 h,于主动脉包裹浸有50%Fe Cl3溶液的滤纸条诱导血栓形成,计算血栓占含血栓的血管湿重百分比。324只SD大鼠随机分成普拉格雷治疗组、阴性对照组和空白组。灌胃给药3 d,末次给药后2 h,麻醉。分离并结扎冠状总动脉,右心室注射月桂酸钠(1 mg/m L)0.2 m L,2 h后,取心脏做病理切片,观察微冠脉血栓形成情况。结果普拉格雷有效提高肺栓塞小鼠存活率,减少Fe Cl3诱导形成血栓的重量,改善月桂酸钠诱导的冠脉血栓形成情况。结论本研究中所建立的几种栓塞模型简单易得,适用于ADP受体拮抗剂类抗栓药效果的评价。
OBJECTIVE To evaluate the effect of Prasugrel in three different embolism models and find out the models that are appropriate for P2Y12 ADP receptor antagonist screening.METHODS 1 20 mice were divided into Prasugrel group and control group random Ly,administrated with Prasugrel and water respectively for 3 d 2 h after the last administration,mixture made by collagen and adrenalin was injected into tail veins,and the viability of mice was figured; 2 16 SD rats were divided into Prasugrel group and control group random Ly,administrated with Prasugrel and water respectively for 3 d. 2 h after the last administration,enclosed filter paper saturated with Fe Cl3 solution,which can induce thrombosis. Then percentage of the thrombus wet weight in the vein was calculated; 316 SD rats were divided into Prasugrel group and control group random Ly,administrated with Prasugrel and water respectively for 3 d.2 h after the last administration,rats were anaesthetized and injection to the right ventricle with sodium laurate were carried out after coronary artery ligation. 2 h later,hearts were taken and pathological sections were made to observe the formation of thrombosis.RESULTS Prasugrel can increase the viability of mice with pulmonary embolism,reduce the weight of thrombus induced by Fe Cl3 solution and at the same time improve the conditions of coronary artery embolism induce by sodium laurate. CONCLUSION The embolism models established in this study are appropriate for screening ADP receptor antagonist.
关键词(KeyWords):
普拉格雷;栓塞;P2Y12ADP受体拮抗剂
Prasugrel;embolism;P2Y12ADP receptor antagonists
基金项目(Foundation):
作者(Author):
孔焕育,程小荣,刘锐锋
KONG Kuanyu,LI Bolan,LIU Ruifeng
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