利伐沙班及其拮抗剂对大鼠出血模型的影响研究.docVIP

利伐沙班及其拮抗剂对大鼠出血模型的影响研究 孙双勇, 李亚丽, 郑海娟, 王维亭, 赵专友* 300193 摘要：目的：研究利伐沙班的出血副作用，并对其拮抗剂的作用进行探索。 方法：大鼠灌胃给予不同剂量利伐沙班(0.3-30 mg/kg)1.5 h后，根据断尾法测定的出血时间与出血量，以及凝固法测定的血浆PT，观察其出血副作用；大鼠灌胃给予大剂量利伐沙班(30 mg/kg)制备出血模型，尾静脉注射人凝血酶原复合物或白眉蛇毒血凝酶，通过测定大鼠断尾出血时间、出血量以及血浆PT，观察两种药物对出血作用的拮抗效果。 结果：大鼠灌胃给予不同剂量的利伐沙班后，出血时间、出血量、血浆PT都明显增加，与利伐沙班的剂量呈正相关；人凝血酶原复合物能够显著抑制利伐沙班所致的出血时间、出血量和血浆PT的增加，而白眉蛇毒血凝酶对上述指标无明显影响。 结论：利伐沙班存在剂量依赖性的出血副作用，在出血严重时，可采用人凝血酶原复合物作为拮抗剂进行治疗。 关键词：利伐沙班、出血副作用、人凝血酶原复合物、拮抗剂 中图分类号： 文献标志码： 文章编号： Effects of rivaroxaban and its antagonists on hemorrhage model in rats SUN Shuang-yong, LI Ya-li, ZHENG Hai-juan, WANG Wei-ting, ZHAO Zhuan-you* Tianjin Centre for New Drug Safety Assessment and Research, Tianjin 300193, China Abstract: Objective: To study the bleeding side effect of rivaroxaban and explore its antagonists. Methods: In the bleeding side effect experiment, rats were intragastric administration of different doses (0.3-30 mg/kg) of rivaroxaban. 1.5 hours after administration, bleeding time and blood loss were determined by tail cutting method, and plasma PT was measured by Kit method. In the antagonist exploration experiment, hemorrhage model of rats was formed by intragastric administration of large doses (30 mg/kg) of rivaroxaban. Human prothrombin complex and hemocoagulase were administration by intravenously injection to observe their antagonistic effect by measuring the bleeding time, blood loss and plasma PT. Results: Bleeding time, blood loss and plasma PT of rats increased significantly after administration of different doses of rivaroxaban, which were positively correlated with the dose of drug. Human prothrombin complex concentrate could weaken the increase of bleeding time, blood loss and plasma PT, while hemocoagulase had no significant effect on these indicators. Conclusion: Rivaroxaban has dose-dependent side effect of bleeding, and human prothrombin complex can alleviate this side effect when severe bleeding happens. Keywords: Rivaroxaban, bleeding side effect, human prothr