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目的研究注射用重组双功能水蛭素(RGD-Hirudin)抗凝防栓的作用。方法选用36只SD大鼠制备股动脉切断吻合模型,随机分成6组,每组6只。1．生理盐水(对照)组。2．肝素钠组(150U/ kg~(-1)·d~(-1))。3．野生型水蛭素组(0．5mg/kg~(-1)·d~(-1))。4．重组双功能水蛭素组(0．1mg/kg~(-1)·d~(-1))。5．重组双功能水蛭素组(0．2mg/kg~(-1)·d~(-1))。6．重组双功能水蛭素组(O．5ms/kg~(-1)·d~(-1))。术前30 min、术后60 min和术后72 h心脏取血,测定血小板聚集率、aPTT、PT、TT和血浆纤维蛋白原的含量。术后3 d,切取吻合口远、近端血管5mm,作病理切片分析。结果重组双功能水蛭素组(0．1mg/kg~(-1)·d~(-1))的血管通畅率与野生型水蛭素组的疗效相同,优于肝素钠组,随着剂量的加大,治疗效果越好,并有明显的量效关系。血液学指标证明：重组双功能水蛭素能抑制血小板聚集,显著延长aPTT、PT和TT,对血浆纤维蛋白原几乎没有影响。结论重组双功能水蛭素具有抗凝血酶和抗血小板聚集双重活性,抗凝、防栓作用强。与野生型水蛭素相比,产生相同治疗效果所需剂量小,疗效优于肝素钠和野生型水蛭素。
Objective To study the anticoagulant and antithrombotic effects of recombinant double-function hirudin (RGD-Hirudin) for injection. Methods Thirty-six SD rats were selected to prepare a femoral artery transection and anastomosis model and randomly divided into 6 groups, 6 in each group. 1. Saline (control) group. 2. Heparin sodium group (150 U/kg~(-1)·d~(-1)). 3. Wild-type hirudin group (0.5 mg/kg~(-1)·d~(-1)). 4. Recombinant bifunctional hirudin group (0.1 mg/kg~(-1)·d~(-1)). 5. Recombinant bifunctional hirudin group (0.2 mg/kg~(-1)·d~(-1)). 6. Recombinant bifunctional hirudin group (O.5ms/kg~(-1)·d~(-1)). Blood was taken from the heart 30 minutes before operation, 60 minutes after operation and 72 hours after operation. Platelet aggregation rate, aPTT, PT, TT and plasma fibrinogen were measured. Three days after operation, the distal and proximal anastomosis vessels were cut 5 mm for analysis of pathological sections. Results The patency rate of the recombinant bifunctional hirudin group (0.1 mg/kg~(-1)·d~(-1)) was the same as that of the wild-type hirudin group, which was superior to that of the heparin group. Increase, the better the treatment effect, and there is a clear dose-effect relationship. Hematological indicators demonstrated that recombinant bifunctional hirudin inhibited platelet aggregation, significantly prolonged aPTT, PT, and TT, with little effect on plasma fibrinogen. Conclusion Recombinant bifunctional hirudin has anti-thrombin and anti-platelet aggregating activity, anticoagulant and anti-thrombotic effects. Compared with wild-type hirudin, the dose needed to produce the same therapeutic effect is small, and the curative effect is better than heparin sodium and wild-type hirudin.