摘要
目的研究重组水蛭素的抗血栓及抗凝作用。方法采用犬冠状动脉内皮损伤与临界狭窄引起犬不稳定型心绞痛模型及大鼠颈动脉电刺激血栓形成模型。结果静脉给予重组水蛭素0.6、2.0、6.0mg/kg,能抑制因狭窄及局部损伤犬冠状动脉引起的血小板依赖性血栓形成,表现在周期性冠状动脉流量降低发生次数呈剂量依赖性减少,分别减少了27.0%、43.6%、55.9%。重组水蛭素具有明显的抗凝作用,0.6、2.0、6.0mg/kg延长犬凝血酶时间(TT)、白陶土活化的部分凝血活酶时间(APTT)。重组水蛭素引起一定程度的出血作用,麻醉犬伤口失血量及黏膜出血时间较肝素钠组稍轻。重组水蛭素对麻醉犬血压及心率无明显影响。静脉给予重组水蛭素0.3、1.0、3.0mg/kg,呈剂量依赖性延长动脉血栓的形成时间,与对照组比较分别延长了22.8%、55.0%、72.0%(P值均<0.01)。结论重组水蛭素具有明显的抗血栓和抗凝作用,对不稳定型心绞痛具有明显的治疗作用。
Objective To examine the antithrombotic and anticoagulant effect of recombinant hirudin（r-HV）. Methods The left circumflex coronary artery was instrumented with a flow probe and critical stenosis, and arterial wall injury was induced by mechanical clip. Cyclic flow reductions were created in 30 dogs. Using electrically induced occlusive thrombus in rat, the effiacy of hirudin on formation of thrombus was measured. Results Dogs was given an intravenous bolus of 2/3 of total doses and followed by infusion over 60 min at the doses of 0.6, 2, 6 mg/kg of r-HV respectively. Cyclic flow reductions were reduced in the dose-dependent mode. TT and APTY was significantly prolonged. Compared with heparin, r-HV has a similar action in antithrombosis and anticoagulation. Blood pressure and heart rate were unchanged, however there was a significant increase in the blood loss. r-HV also significantly delayed time to occlusive common carotid artery thrombosis in rat.Concluslon The results suggest that r-HV is an effective antithrombosis and anticoagulant agent and may offer a therapeutic alternative to current antithrombosis in the management of unstable angina.
出处
《中国药物与临床》
CAS
2006年第5期346-349,共4页
Chinese Remedies & Clinics
