一种来自于尖吻蝮蛇毒的新类凝血酶对血液止血机制的研究

Study of hemostasic mechanism of a novel thrombin-like enzyme from Deinagkistrodon acutus snake venom on the blood system

目的：研究尖吻蝮蛇蛇毒止血酶Agacutase的止血机制。方法：水蛭素、肝素、苯甲基磺酰氟（PMSF）、钙离子或尿素等分别与Agacutase酶混合,在体外研究它们对酶凝结活性的影响。新西兰白兔静脉注射Agacutase,观察新西兰白兔的血凝和纤溶指标。结果：水蛭素和肝素对该酶没有影响,PMSF和尿素明显抑制酶的凝结活性,而钙离子激活酶凝结活性。静脉注射Agacutase 0.03-0.12 U/kg剂量后,各组全血凝固时间与给药前相比均有不同程度的缩短,给药后2 h药效达高峰,药效持续24 h。与给药前比较,各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,对活化部分凝血活酶时间（APTT）无影响。结论：Agacutase在血管内引起较高浓度的可溶性纤维蛋白,但不激活凝血因子II和XIII,在伤口部位加速止血。在正常的血管内,不会造成血栓形成。所有实验结果显示,Agacutase是一个有效的潜在止血剂。

AIM： To study the hemostasic mechanism of Agacutase on blood system. METHODS： Heparin,hirudin,PMSF,calcium,or urea was mixed with Agacutase respectively and the enzyme activity were observed. The blood coagulation and fibrinolysic parameters in New Zealand white rabbits were observed after iv Agacutase. RESULTS： Hirudin or heparin had no effect on the enzyme activity. PMSF or urea inhibited the enzyme activity obviously whereas calcium activated the activity. 0. 03-0. 12 U / kg dose of Agacutase induced the shortening of the rabbit blood clotting times on the manner of time and dose. The peak effect occurred at 2 h after administration and the hemostatic effect kept for 24 h. The rabbit blood fibrinogen concentrations and blood viscosity showed similar changes with the blood coagulation times. The result showed that Agacutase did not influence the APTT time. CONCLUSION： Agacutase induces higher concentrations of soluble fibrin in the blood vessels and accelerates hemostasis at the wound site. It does not activate the Factors II or XIII to cause thrombosis in blood vessels. All the results show that Agacutase is a potential hemostasic compound.