摘要
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 A novel reeombinant anticoagulant RGD-Hirudin （RDC,-Hirudin） has been available. The purpose of this research was to study its anti-thrombotie effeet in artery anastomosis. Methods Femoral artery transeetion and anastomosis model was established in 36 Sprague Dawley rats. These rats were then randomized into 6 groups and given normal saline, 150U/kg/d heparin, 0.5mg/kg,/d wt-Hirudin, 0. 1mg/kg/d RGD-Hirudin, 0.2mg/ kg/d RGD-Hirudin, and 0.5mg/kg/d RGD-Hirudin respeetively. TT, PT, aPTT, maximum platelet aggregation （PAGm） indueed by ADP and plasma eoneentration of fibrinogen were determined 30 minutes before and 1 and 72 hours after the surgery. Results Vessel patency rate in 0.1mg/kg/d RGD-Hirudin group was similar to that of wt-Hirudin group and higher than that of heparin group. The higher the dosage of RGD-Hirudin, the better the pateney rate. TT, PT and aPTT were prolonged after infusion of RGD-Hirudin, wt-Hirudin or heparin. Only RGD-Hirudin was eapable of inhibiting PAGm. Histopathologieal results showed that the dosage of RGD-Hirudin for prevention of thrombosis was half to one third of the dose of wt-Hirudin. Furthermore, no bleeding eomplieation was observed in RGD-Hirudin treatment rats, in contrast to those treated with wt-Hirudin or heparin. Conclusion RGD-Hirudin has both antieoagulant and antithrombotic effeets.Comparod to wt-Hirudin, smaller dosage of RGD- Hirudin is needed to aehieve similar effeet. It has better therapeutic effect than heparin and wt-Hirudin.
出处
《中华手外科杂志》
CSCD
北大核心
2006年第2期106-108,共3页
Chinese Journal of Hand Surgery
基金
上海市现代生物与新药发展基金(20014319202)
关键词
重组双功能水蛭素
抗凝防栓
动物
实验
Recombinant RGD-Hirudin
Anti-thrombotic effect
Animals, laboratory
