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一个新的尖吻蝮蛇类凝血酶对血液活性的研究 被引量:16

Pharmacodynamics of Agacutin: a thrombin-like enzyme from Agkistrodon acutus
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摘要 目的研究蛇毒类凝血酶Agacutin的止血效果。方法新西兰白兔静脉注射Agacutin,观察新西兰白兔的血凝和纤溶指标;小鼠皮下注射,采用小鼠剪尾试验测定其止血效果。结果静脉注射Agacutin0.01~0.05U·kg-1剂量后,各剂量组全血凝固时间与给药前相比均有不同程度的缩短(44.9%~60.5%),给药后30min药效达高峰,药效持续24h。与给药前比较,各实验组兔血纤维蛋白原含量和血黏度在给药后有不同程度的降低,这与血液凝固时间缩短一致。试验结果显示,Agacutin对活化部分凝血活酶时间、血小板数量、血小板释放活性均无明显影响,但对优球蛋白溶解时间有不同的缩短,显示有弱的溶栓活性。腹腔注射Agacutin0.5~2.0U·kg-1剂量后,小鼠剪尾出血时间有不同程度的缩短(24%~66%)。结论Agacutin在血管内引起较高浓度的可溶性纤维蛋白和不激活凝血因子Ⅱ和,当有伤口时,在伤口部位加速止血,在正常的血管内,不会造成不溶性纤维蛋白和血栓的形成。所有实验结果显示,Agacutin是一个有效的潜在止血剂。 Objective To investigate the effects of Agacutin on blood system and evaluate its hemostatic action in animals. Methods The indexes on blood coagulation and fibrinolysis system were determined after Agacutin was administerted intravenously, with blood samples taken by cardiac puncture. The hemostatic effect was expressed in terms of the mouse tail bleeding time. Results Intravenous injection of Agautin 0.01 - 0.05 U· kg^-1 could markedly shorten the rabbit blood coagulation time by 44.9% - 60.5% and the effect lasted for 24 h. When Reptilase and Agacutin were administered in the same dosage, their effects on blood coagulation were about equal in strength and duration. After Agacutin iv, the rabbit blood fibrinogen level and blood viscosity were decreased, which persisted in parallel with the shortening of blood coagulation time. Experimental results also showed that Agacutin had no influence on activated partial thromhoplastin time (APTT), platelet count, platelet releasing activity, platelet in vitro aggregation, and euglobulin coagulation time (ECT). But the shortening of euglobulinolysis time (ELT) suggested that Agacutin have a weak fibrinolytic activity. Intraperitoneal administration of Agacutin 0.5 - 2.0 U· kg^-1 could shorten the mouse tail bleeding time by 24% - 66%. Conclusion Tne results show that Agacutin elevates the level of soluble fibrin in blood vessel and does not activate prothrombin (factor Ⅱ) or factor Ⅻ. Agacutin promotes hemostasis only when there is a cut or bleeding. The soluble fibrin induced in normal vessel will not form insoluble fibrin clot or thrombosis in vivo. The present study shows that Agacutin is a potential hemostatic agent, having no undesirable effects on otherwise normal bload coagulation.
出处 《徐州医学院学报》 CAS 2005年第4期308-312,共5页 Acta Academiae Medicinae Xuzhou
基金 深圳易合康生物技术开发有限公司 广东燕塘生物化学药业有限公司和南方医科大学中心实验室等单位资助
关键词 类凝血酶 止血剂 尖吻蝮蛇 蛇毒 血液凝固 Agacutin 药效学 thrombin- like enzyme coagulant Agkistrodon acutus snake venom blood coagulation Agacutin pharmacodynamics
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