Antithrombotic efficacy of a recombinant nematode anticoagulant peptide (rNAP5) in canine models of thrombosis after single subcutaneous administration.
Antithrombotic efficacy of a recombinant nematode anticoagulant peptide (rNAP5) in canine models of thrombosis after single subcutaneous administration.
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发表时间：
1997-10
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通讯作者：
S. Rebello;H. S. Blank;W. Rote;G. Vlasuk;B. Lucchesi
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作者：
S. Rebello;H. S. Blank;W. Rote;G. Vlasuk;B. Lucchesi
我们描述了重组线虫抗凝肽(RNAP5)的抗血栓作用，重组线虫抗凝肽是一种选择性和直接的Xa因子抑制剂。犬动脉和静脉血栓模型的给药。初步评价rNAP5对清醒犬的全身抗凝作用。剂量(0.03、0.1和0.3 mg/kg)可使活化凝血时间和活化部分凝血活酶时间呈剂量依赖性增加。用生理盐水或rNAP5(0.03、0.1和0.3 mg/kg)皮下注射麻醉犬，观察rNAP5的抗血栓作用。在电化学性损伤冠状动脉左回旋支前1小时给药。生理盐水组(n=10)左回旋支在79+/-9min内闭塞，5只动物因室颤而猝死。RNAP5 0.03 mg/kg(163±/-62 min)和0.1 mg/kg(327±/-62)mg/kg治疗组(n=6)均显著延长血管闭塞时间。0.3 mg/kg组(n=5)损伤血管全部通畅8h。与对照组相比，rNAP5治疗组的血栓质量呈剂量依赖性减少，死亡率也较低。0.03和0.1 mg/kg的rNAP5不改变出血时间，而0.3 mg/kg的rNAP5使出血时间增加5倍。在另一项研究中，我们评估了rNAP5(0.1 mg/kg)预防颈动脉和颈静脉血栓形成的效果。对于内皮损伤，生理盐水组(n=6)的颈动脉和颈静脉分别在142+/-16和100+/-11min内闭塞，而rNAP5保持了颈动脉(6/6)和颈静脉(5/6)的血管通畅，并显著降低了血栓重量。结果表明，rNAP5在犬动、静脉血栓形成模型中具有抗血栓作用。行政管理。
We describe the antithrombotic effects of recombinant nematode anticoagulant peptide (rNAP5), a selective and direct factor Xa inhibitor, after a single s.c. administration in canine models of arterial and venous thrombosis. The systemic anticoagulant effects of rNAP5 were evaluated initially in conscious dogs after s.c. dosing (0.03, 0.1 and 0.3 mg/kg) that resulted in a dose-dependent increase in the activated clotting time and the activated partial thromboplastin time. The antithrombotic effects of rNAP5 were evaluated in anesthetized dogs where saline or rNAP5 (0.03, 0.1 and 0.3 mg/kg s.c.) was administered 1 hr before the left circumflex coronary artery was subjected to electrolytic injury. In the saline group (n = 10), the left circumflex artery occluded in 79 +/- 9 min, and 5 of 10 animals progressed to sudden death due to ventricular fibrillation. rNAP5 significantly prolonged the time to occlusion in the 0.03 mg/kg (163 +/- 62 min) and 0.1 mg/kg (327 +/- 62) treatment groups (n = 6). In the 0.3 mg/kg group (n = 5), all of the injured vessels remained patent for 8 hr. There was a dose-dependent reduction in the thrombus mass in the rNAP5-treated animals as compared with controls, as well as a lower mortality rate. rNAP5, in the doses of 0.03 and 0.1 mg/kg, did not alter the bleeding time, whereas 0.3 mg/kg produced a 5-fold increase. In a separate study, we evaluated the efficacy of rNAP5 (0.1 mg/kg) in the prevention of carotid artery and jugular vein thrombosis. In response to endothelial injury, the carotid artery and jugular vein in the saline group (n = 6) occluded in 142 +/- 16 and 100 +/- 11 min, respectively, compared with rNAP5, which maintained vessel patency in the carotid artery (6/6) and jugular vein (5/6) and significantly decreased the thrombus weights. The results demonstrate that rNAP5 has antithrombotic efficacy in canine models of arterial and venous thrombosis after a single s.c. administration.