大剂量尿激酶溶凝的量效时效及安全性的初步研究  

Preliminary study of dose-time-effect of clot lysis and its safety with a large dose urokinase in vitro

作　　者：王成东[1] 武丽丽[1] 王永和[1] 王玉亭[1] 王喆[1] 

机构地区：[1]山东省潍坊市人民医院中心实验室,261041

出　　处：《中国实用医药》2008年第13期3-5,共3页China Practical Medicine

基　　金：山东省潍坊市卫生科技发展计划课题(项目编号:200408)

摘　　要：目的探讨尿激酶溶解血凝块的最佳用药剂量、用药时机及药物最佳作用时间，为临床一次性清除血肿提供实验依据。方法采用2个（4×4）拉丁方设计，分析UK剂量[（1万U／ml、2万U／ml、3万U／ml、4万U／ml）]、用药时机（抽血后2、4、8、16h）和药物作用时间（加UK后2、4、8、16h）对溶凝效果的影响。制备家兔脑内血肿模型，对比观察不同剂量尿激酶（10000U vs 30000U）及等量生理盐水对脑组织形态学的影响。结果UK剂量对溶凝体积的差异有统计学意义（F=9、58，P=0．0105），尿激酶10000U组的溶凝体积明显低于20000U组、30000U组或40000U组，而后3组间的差异无统计学意义。用药时机和药物作用时间对溶凝体积的差异均无统计学意义（F=1．83，P=0．2423；F=2．39，P=0．1673）。光学显微镜和电子显微镜结果显示，3组标本均出现脑出血后急性期的形态学改变，未见其他的细胞形态和超微结构方面的异常改变。结论UK剂量是影响溶凝效果的关键因素，20000～30000U／ml的UK为最佳安全剂量。延迟16h用药不影响溶凝效果，UK作用2h足以发挥溶凝效用。Objective To explore the optimal dose and time for clot lysis with urokinase for further providing experimental basis for the complete resolution of intracerebral solid hematoma one-off. Methods According to the 4×4 Latin Square design,lytic efficacy was assessed in UK dose[ （ 10 000 U/ml,20 000 U/ml,30 000 U/ml or 40 000 U/ml）] and the timing of Uk infusion（2,4,8,16 h after blood sample taken）and UK lytic time（2,4,8,16 h after UK infusion）in vitro, 15 rabbits were subjected to the intracerebral hematoma model for analysing the effect of 2 differents UK dose（ 10 000 U vs 30 000 U） on brain tissue around hematoma cavity. Resalts Significant difference（F = 9.58 ,P = 0. 010 5 ）of lytic efficacy of UK was noted with UK different dose treatment series,and lytic volume（ 101.25μl）was significantly decreased with 10 000 U/ml UK treatment compared with other three series （233.50,237.25,317.25 μl）, but no significant difference was found among the three or in UK infusion timing （ F = 1.83, P = 0. 2423 ） or lytic time （ F = 2.39, P = 0. 167 3 ）. The results in morphology showed pathological changes on acute phase of cerebral hemorrhage, some abnormal changes in cell shape and uhrastructure such as degeneration or necrosis were not observed. Conclusion The results suggest that UK dose is the key for lytic efficacy,and the optimal and safe dose of UK required to lyse 1 ml of clotted blood would be 20 000-30 000 U/ml. Delaying therapy of up to 16 hours does not significantly compromise its efficacy,and 2 hours are quite sufficient for receiving good lytic efficacy with UK treatment.

关 键 词：大剂量尿激酶 血凝块溶解 兔 量效时效 

分 类 号：R651.1[医药卫生—外科学] R595.4[医药卫生—临床医学]