大剂量尿激酶溶凝的量效时效及安全性的初步研究(1)
【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、16 h)和药物作用时间(加UK后2、4、8、16 h)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(10 000 U vs 30 000 U)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=0.010 5)，尿激酶10 000 U组的溶凝体积明显低于20 000 U组、30 000 U组或40 000 U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=0.242 3；F=2.39,P=0.167 3)。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，20 000~30 000 U/ml的UK为最佳安全剂量。延迟16 h用药不影响溶凝效果，UK作用2 h足以发挥溶凝效用。
, http://www.100md.com
【关键词】大剂量尿激酶；血凝块溶解；兔；量效时效
Preliminary study ofdose-time-effect of clot lysisand its safety with a large dose urokinase in vitro
WANG Cheng-dong,WU Li-li,WANG Yong-he,et al.Department of Center Laboratory,Weifang Peoples Hospital,Weifang 261041,China
【Abstract】 Objective To explore the optimal dose and time for clot lysis with urokinase for further providing experimental basis for the complete resolution of intracerebral solidhematoma one-off.
, http://www.100md.com
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.Results 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(101.25 μl)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 ultrastructure 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.
, 百拇医药
【Key words】Large dose urokinase; Clot lysis；Rabbits; Dose-time effect
在脑出血的外科治疗中，传统的尿激酶(urokinase,UK)溶解引流术是尽快清除血肿、改善患者预后的有效方法，但治疗效果仍然不甚令人满意，其主要原因之一是对UK溶凝的量效与时效知之甚少[1]。笔者对尿激酶溶解血肿较佳的用药时机、用药剂量、药物作用时间及用药安全性等问题进行研究，现报告如下。
1 材料与方法
1.1 UK来源 UK为北京赛生药业有限公司产品，为冻干品，用0.9%灭菌生理盐水配成10 000、20 000、30 000、40 000 U/ml溶液。即用即配。
1.2 血凝块制备 试验血凝块来自我院神经外科高血压脑出血患者。术前静脉抽血20 ml，每管1 ml分装， 立即置于37℃水浴中温育2~16 h。按用药时机(抽血后2、4、8、16 h)分为4组，每组5支试管，1支为对照管，另外4支为试验管。
1.3 实验方法 根据2个(4×4)拉丁方设计，分别于抽血后2、4、8、16 h，注入1 ml浓度为10 000、20 000、30 000、40 000 U/ml的UK溶液(试验管)或等体积0.9%灭菌生理盐水(对照管)，再分别于加酶后2、4、8、16 h测定试验管血凝块体积(μl)。对照管与试验管血凝块体积的差值为UK溶凝体积，其值越大，溶凝效果越好。血凝块体积测量参考“血块收缩试验”，将血凝块取出后，用数字可调式移液器精确测量残留液体积，间接计算血凝块体积。, 百拇医药(王成东 武丽丽 王永和 王玉亭 王 喆)
, http://www.100md.com
【关键词】大剂量尿激酶；血凝块溶解；兔；量效时效
Preliminary study ofdose-time-effect of clot lysisand its safety with a large dose urokinase in vitro
WANG Cheng-dong,WU Li-li,WANG Yong-he,et al.Department of Center Laboratory,Weifang Peoples Hospital,Weifang 261041,China
【Abstract】 Objective To explore the optimal dose and time for clot lysis with urokinase for further providing experimental basis for the complete resolution of intracerebral solidhematoma one-off.
, http://www.100md.com
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.Results 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(101.25 μl)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 ultrastructure 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.
, 百拇医药
【Key words】Large dose urokinase; Clot lysis；Rabbits; Dose-time effect
在脑出血的外科治疗中，传统的尿激酶(urokinase,UK)溶解引流术是尽快清除血肿、改善患者预后的有效方法，但治疗效果仍然不甚令人满意，其主要原因之一是对UK溶凝的量效与时效知之甚少[1]。笔者对尿激酶溶解血肿较佳的用药时机、用药剂量、药物作用时间及用药安全性等问题进行研究，现报告如下。
1 材料与方法
1.1 UK来源 UK为北京赛生药业有限公司产品，为冻干品，用0.9%灭菌生理盐水配成10 000、20 000、30 000、40 000 U/ml溶液。即用即配。
1.2 血凝块制备 试验血凝块来自我院神经外科高血压脑出血患者。术前静脉抽血20 ml，每管1 ml分装， 立即置于37℃水浴中温育2~16 h。按用药时机(抽血后2、4、8、16 h)分为4组，每组5支试管，1支为对照管，另外4支为试验管。
1.3 实验方法 根据2个(4×4)拉丁方设计，分别于抽血后2、4、8、16 h，注入1 ml浓度为10 000、20 000、30 000、40 000 U/ml的UK溶液(试验管)或等体积0.9%灭菌生理盐水(对照管)，再分别于加酶后2、4、8、16 h测定试验管血凝块体积(μl)。对照管与试验管血凝块体积的差值为UK溶凝体积，其值越大，溶凝效果越好。血凝块体积测量参考“血块收缩试验”，将血凝块取出后，用数字可调式移液器精确测量残留液体积，间接计算血凝块体积。, 百拇医药(王成东 武丽丽 王永和 王玉亭 王 喆)