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[摘要]
目的 研究多肽衍生物L(fēng)X2416的抗血栓形成作用。方法 通過凝血酶原時間(PT)、部分活化凝血酶原時間(APTT)測定,考察LX2416對凝血系統(tǒng)的影響。通過二磷酸腺苷(ADP)誘導(dǎo)的體外血小板聚集實驗,考察LX2416的抗血小板聚集作用。采用SD大鼠隨機分為對照組、替羅非班(1.0 mg/kg)組、LX2416(0.3、1.0、3.0 mg/kg)組,通過動靜脈旁路血栓模型,考察LX2416體內(nèi)的抗血栓作用。采用ICR小鼠隨機分為對照組、替羅非班(1 mg/kg)組、LX2416(1、3、10 mg/kg)組,通過出血毒性實驗,考察LX2416的出血風(fēng)險。結(jié)果 LX2416對PT、APTT無顯著性影響,能夠抑制ADP誘導(dǎo)的體外血小板聚集和大鼠動靜脈旁路血栓形成,呈劑量相關(guān)性。LX2416具有一定的出血風(fēng)險,但比替羅非班出血風(fēng)險要低。結(jié)論 LX2416通過抑制血小板聚集,具有良好的抗血栓形成作用,并且出血風(fēng)險較低。
[Key word]
[Abstract]
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.
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