目的 研究利伐沙班的出血副作用,并對(duì)其拮抗劑對(duì)大鼠出血模型的影響進(jìn)行探索.方法 大鼠ig給予不同劑量利伐沙班(0.3～30 mg/kg)1.5 h后,根據(jù)斷尾法測(cè)定的出血時(shí)間、出血量,以及凝固法測(cè)定的血漿凝血酶原時(shí)間(PT),觀察其出血副作用;大鼠ig給予大劑量利伐沙班(30 mg/kg)制備大鼠出血模型,尾iv人凝血酶原復(fù)合物或白眉蛇毒血凝酶,通過(guò)測(cè)定大鼠斷尾出血時(shí)間、出血量以及血漿PT,觀察兩種藥物對(duì)出血作用的拮抗效果.結(jié)果 大鼠ig給予不同劑量的利伐沙班后,出血時(shí)間、出血量、血漿PT都明顯增加,與利伐沙班的劑量呈正相關(guān);人凝血酶原復(fù)合物能夠顯著抑制利伐沙班所致的出血時(shí)間、出血量和血漿PT的增加,而白眉蛇毒血凝酶對(duì)上述指標(biāo)無(wú)明顯影響.結(jié)論 利伐沙班存在劑量相關(guān)性的出血副作用,在出血嚴(yán)重時(shí),可采用人凝血酶原復(fù)合物作為拮抗劑進(jìn)行治療.

Objective To study the bleeding side effect of rivaroxaban and explore its antagonists on hemorrhage model in rats. Methods In the bleeding side effect experiment, rats were ig administered with different doses (0.3 — 30 mg/kg) of rivaroxaban. Bleeding time and blood loss were determined by tail cutting method, and plasma prothrombin time (PT) was measured by Kit method 1.5 h after administration. In the antagonist exploration experiment, hemorrhage rat model was established by ig administration of large dosage (30 mg/kg) of rivaroxaban. Human prothrombin complex and hemocoagulase were given by iv injection and their antagonistic effect was observed 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.

天津市應(yīng)用基礎(chǔ)與前沿技術(shù)研究計(jì)劃青年項(xiàng)目(14JCQNJC13300)