人胎盘抗凝蛋白变体的抗凝与抗栓作用

A study of human annexin Ⅴ derivative: its effects of anticoagulation and antit hrombosis

探索新型抗凝蛋白质———人胎盘抗凝蛋白变体 (annexinⅤderivative,AND)抗凝和抑制动脉血栓形成的作用。方法 比较实验组动物和对照组动物在用药前 ,用药后 15 ,30 ,6 0min及停药 2h活化部分凝血活酶时间 (APTT)、凝血酶原时间 (PT)、凝血酶时间 (TT)、血浆纤维蛋白原 (Fg)含量。用药 15min后用球囊剥脱股动脉内皮并监测股动脉远端的血压 ,记录脉压为 0的时间即血栓完全闭塞血管的时间。最后剪取球囊损伤的股动脉 ,测量所形成血栓的长度、血栓的湿重和干重。结果 抗凝指标 :用药组在用药后 15min时 ,其APTT值最长 ,且APTT值明显长于生理盐水组 (P <0 .0 5 ) ,短于肝素组 (P <0 .0 1) ,肝素组的APTT、TT值明显长于其他 3组 ,PT值各组间差异无统计学意义 ;对Fg的影响 :大剂量用药组似乎可以降低Fg的血浆含量 ;血栓质量 :无论是湿重还是干重AND组都明显轻于对照组 (P <0 .0 0 1) ,大剂量AND组血栓干重显著轻于小剂量组 (P <0 .0 5 ) ;小剂量AND组血栓的长度明显短于生理盐水组 (P <0 .0 5 ) ,但和肝素组相比 ,差异无统计学意义 (P =0 .4 85 ) ,大剂量AND组明显短于生理盐水组 (P <0 .0 1)和肝素组 (P <0 .0 5 ) ;脉压为 0的时间 :AND组显著长于对照组 (P <0 .0 5 )和肝素组相比 ,差异无统计学意义。结?

Objective To investigate the effects of a new anticoagulant, annexin Ⅴ derivative (AND) o n anticoagulation and antithrombosis. Methods High and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bol us injections followed by half the respective AND doses by iv infusion over 2 ho urs. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) an d fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm×15 mm balloon was put into fem oral artery to induce endothelial denudation 15 min after Ⅳ bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occlued completely by a thrombus. The femoral arteries w ere collected and the thrombi were stripped off for measuring their lengths, wet and dry weights. Results Anticoagulation parameters: APTT at 15 mi n after iv bolus in AND group was significantly longer than that in group 4 ( P< 0.05) but shorter than that in group 3 (P<0.05); APT T and TT in group 3 were significantly longer than those in groups 1, 2 and 4. F ibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis valuse: the w et and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P<0.05). The dry weight in high-dose AND group was remar kably lighter than that in low-dose group (P=0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 ( P=0.013), but not for group 3 (P>0.05). It was remarkably s horter in high-dose AND group than in both group 3 (P<0.001) and 4 (P=0.015). The time when pulse pressure equaled to 0 was longer in A ND group than in group 4 (P<0.05), but not in 3. Conclusion AND is an effective anticoagulant and antithrombosis agent, the highest an ticoagulation effect occurs at 15 min after Ⅳ bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.