人胎盘抗凝蛋白变体抗凝与抗血栓形成的效应 与作用时间及剂量的关系(英文)  

Effects of human annexin V derivative on coagulation and thrombosis Effective time and dosage

作　　者：崔俊友[1] 王连生[2] 鞠成伟[2] 杨翔[3] 华子春[3] 

机构地区：[1]江阴市人民医院心脏科,江苏省江阴市214400 [2]南京医科大学第一附属医院心脏科,江苏省南京市210029 [3]南京大学生命科学院,江苏省南京市210093

出　　处：《中国临床康复》2005年第27期192-194,共3页Chinese Journal of Clinical Rehabilitation

基　　金：江苏省科委资助项目(01KJB320005)~~

摘　　要：背景:肝素作为最常用的抗凝药物已广泛用于临床,但其存在明显的出血副作用,与纤维蛋白结合的凝血酶活性作用有限,并发血小板减少症等不良反应。将水蛭素C端结构域与人胎盘抗凝蛋白连接在一起构建抗凝蛋白人胎盘抗凝蛋白变体,比较其抗凝抗栓作用与肝素的差异。目的:观察抗凝蛋白质人胎盘抗凝蛋白变体抗凝和抑制动脉血栓形成的作用的量效与时效关系,并了解该药的安全性。设计:完全随机分组设计,对照实验。单位:一所市级医院心脏科。材料:实验于2000-07/2001-04在江苏省人民医院动物实验室完成。选用纯种雄性新西兰白兔32只,随机将白兔分成4组:人胎盘抗凝蛋白变体大剂量组、人胎盘抗凝蛋白变体小剂量组、普通肝素组和生理盐水组,每组8只。方法:肝素和人胎盘抗凝蛋白变体都用生理盐水稀释。①人胎盘抗凝蛋白变体大剂量组:人胎盘抗凝蛋白变体0.7mg/kg静脉推注,继以0.35mg/(kg·h)维持静脉滴注2h;人胎盘抗凝蛋白变体小剂量组:人胎盘抗凝蛋白变体0.3mg/kg静脉推注,继以0.15mg/(kg·h)维持静脉滴注2h;普通肝素组:肝素75IU/kg静脉推注后,以37.5IU/(kg·h)维持静脉滴注2h;生理盐水组:采用与药物组相同体积的生理盐水和给药方法。②分别在用药前,用药后15和30及60min及停药后2h从股静脉采血测血常规、活化部分凝血活酶时间、凝血酶时间。③用药后15min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即血栓完全闭塞血管的时间。最后剪取球囊损伤的股动脉,剥离血管测量所形成血栓的长度、血栓的湿质量和干质量。④人胎盘抗凝蛋白变体毒副作用观察:实验过程中监测动物的血压、心率、呼吸等生命体征,并将部分动物实验后,行腹部解剖,观察内脏出血的情况,检测血白细胞数目。主要观察指标:①人胎盘抗凝蛋白变体对凝血系统和血栓形�BACKGROUND： As a common anticoagulant, heparin is widely used in clinic, but it has remarkable side effects such as severe bleeding and heparin-induced thrombocytopenia, and it cannot inactivate fibrin-bound thrombin. Annexin V derivative （AND） is inosculated with C-terminal of hirudin and annexin V, and its anticoagulation and anti-thrombosis effects are compared with those of heparin. OBJECTIVE： To investigate the relationship between quantitative effectiveness and time effectiveness of AND on coagulation and thrombosis, and study its reliability. DESIGN： Completely randomized grouping design and controlled study. SETTING： Cardiac Department of a municipal hospital. MATERIALS： The experiment was conducted at the Animal Laboratory of Jiangsu Provincial People＇s Hospital from July 2000 to April 2001. Totally 32 male New Zealand white rabbits were randomly divided into 4 groups, name｜y, high dosage AND group, low dosage AND group, common heparin group and saline group with 8 in each group. METHODS： Heparin and AND were diluted with saline. ① High dosage AND group： 0.7 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.35 mg/（kg ·h） for 2 hours. Low dosage AND group： 0.3 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.15 mg/（kg·h） for 2 hours. Heparin group： 75 IU/kg heparin was injected intravenously and followed by intravenous dripping of 37.5 IU/（kg·h） for 2 hours. Saline group： The same volume of saline and medication were used as those in drug groups. ② Blood sample was collected from the femoral vein before administration so as to test blood routine, activated partial thromboplastin time （APTT） and prothrombin time （PT） after 15-, 30- and 60-minute administration and 2-hour withdrawal. ③ Saccule was separated from endothelium of femoral artery to measure blood pressure of distal femoral artery at 15 minutes after administration. Time of pulse pressure equal to 0 mmHg was recorded when the vessel

关 键 词：钙磷脂结合蛋白V 抗凝药 血栓形成 

分 类 号：R55[医药卫生—血液循环系统疾病]