Université de Paris, Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France.
Université de Paris, Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France; Service d'Hématologie Biologique, AH-HP, Georges Pompidou European Hospital, F-75015 Paris, France.
Prostaglandins Leukot Essent Fatty Acids. 2019 Oct;149:46-51. doi: 10.1016/j.plefa.2019.08.002. Epub 2019 Aug 8.
Discrepancies in preclinical studies of aspirin (ASA) antiplatelet activity in mouse models of bleeding and arterial thrombosis led us to evaluate commonly reported methods in order to propose a procedure for reliably measuring the effects of single dose ASA on mouse hemostasis. FVB and C57Bl6 mice received 100 mg/kg of ASA or vehicle orally 30 min or 3 h prior to investigate either hemostasis using the tail bleeding assay or carotid thrombosis induced by FeCl, or to blood sampling for isolated platelet aggregation and TXB generation. Expected inhibition of COX1 by ASA was ascertained by a strong decrease in TXB production, and its effect on platelet function and hemostasis, by decreased collagen-induced aggregation and increased bleeding time, respectively. Strikingly, we determined that anti-hemostatic effects of ASA were more predictable 30 min after administration than 3 h later. Conversely, ASA did not alter time to arterial occlusion of the carotid upon FeCl-induced thrombosis, suggesting ASA not to be used as reference inhibitor drug in this model of arterial thrombosis.
阿司匹林（ASA）在出血和动脉血栓形成的小鼠模型中的抗血小板活性的临床前研究存在差异，这促使我们评估了常用的方法，以便提出一种可靠测量单次剂量 ASA 对小鼠止血作用的程序。FVB 和 C57Bl6 小鼠在使用尾出血测定法研究止血或用 FeCl 诱导颈动脉血栓形成之前，或在采血用于分离血小板聚集和 TXB 生成之前，分别给予 100mg/kg 的 ASA 或载体口服 30 分钟或 3 小时。ASA 对 COX1 的预期抑制作用通过 TXB 生成的强烈减少来确定，其对血小板功能和止血的影响分别通过胶原诱导的聚集减少和出血时间增加来确定。值得注意的是，我们确定 ASA 的抗止血作用在给药 30 分钟后比 3 小时后更具可预测性。相反，ASA 并没有改变 FeCl 诱导的颈动脉血栓形成时动脉闭塞的时间，这表明 ASA 不能在这种动脉血栓形成模型中作为参考抑制剂药物使用。
