多肽衍生物LX2416抗血栓形成作用研究

目的研究多肽衍生物LX2416的抗血栓形成作用。方法通过凝血酶原时间(PT)、部分活化凝血酶原时间(APTT)测定,考察LX2416对凝血系统的影响。通过二磷酸腺苷(ADP)诱导的体外血小板聚集实验,考察LX2416的抗血小板聚集作用。采用SD大鼠随机分为对照组、替罗非班(1.0 mg/kg)组、LX2416(0.3、1.0、3.0 mg/kg)组,通过动静脉旁路血栓模型,考察LX2416体内的抗血栓作用。采用ICR小鼠随机分为对照组、替罗非班(1 mg/kg)组、LX2416(1、3、10 mg/kg)组,通过出血毒性实验,考察LX2416的出血风险。结果 LX2416对PT、APTT无显著性影响,能够抑制ADP诱导的体外血小板聚集和大鼠动静脉旁路血栓形成,呈剂量相关性。LX2416具有一定的出血风险,但比替罗非班出血风险要低。结论 LX2416通过抑制血小板聚集,具有良好的抗血栓形成作用,并且出血风险较低。

Antithrombotic effect of polypeptide derivative LX2416

Objective To study the antithrombotic effect of polypeptide derivative LX2416. Methods Effect of LX2416 on coagulation system was evaluated by PT/APTT assay. Effect of LX2416 on platelet aggregation was observed by the platelet aggregation assay induced by ADP in vitro. SD rats were randomly divided into control group, tirofiban (1.0 mg/kg) group, and LX2416 (0.3, 1.0, and 3.0 mg/kg) groups, and the antithrombotic effect of LX2416 was evaluated by the model of arteriovenous shunt thrombosis. ICR mice were randomly divided into control group, tirofiban (1 mg/kg) group and LX2416 (1, 3, and 10 mg/kg) groups. The bleeding risk of LX2416 was evaluated by bleeding toxicity assay. Results LX2416 had no significant effect on PT/APTT, but could inhibit the platelet aggregation induced by ADP in vitro and the thrombus formation in rats in a dose-dependent manner. Compared with tirofiban, LX2416 had lower bleeding risk. Conclusion LX2416 has good antithrombotic effect by inhibiting platelet aggregation with low bleeding risk.