乌司他丁对体外循环中激活的白细胞和血小板作用的研究

Effects of Urinary Protease Inhibitor on Activated Leukocytes and Platelets during Extracorporeal Circulation

目的研究体外循环(extracorporeal circulation,ECC)下心脏直视手术中乌司他丁对激活的白细胞和血小板功能的作用。方法30例择期ECC下冠状动脉搭桥患者随机分为两组:对照组(C组,n=15)和乌司他丁组(U组,n=15)。对照组ECC中不给予乌司他丁,试验组围ECC期给予乌司他丁100万单位(其中30万为麻醉诱导前给予,40万预充ECC机内,30万为开放升主动脉后给予)。分别于麻醉诱导后(T1)、阻断升主动脉后30 min(T2)、再灌注3 h(T3)、6 h(T4)及12 h(T5)各时间点取静脉血测定中性粒细胞弹性蛋白酶(PMNE)的水平;并于麻醉诱导后(Ta)、ECC结束后给鱼精蛋白前(Tb)、鱼精蛋白中和后1 h(Tc)、术后24 h(Td)提取全血标本测定CD62p的表达。此外,于ECC前、后抽取动脉血气监测肺泡动脉血氧梯度(A-aDO2)。结果两组血清中PMNE的浓度在T2、T3、T4、T5各时间点都明显高于T1时间点(P<0.01),U组的PMNE水平明显低于对照组(P<0.05)。Tb、Tc、Td时间点两组CD62p的表达明显高于Ta时间点,但是两组之间没有明显差异。相比较对照组,U组的A-aDO2明显低于对照组,且患者机械通气时间低于对照组。结论在ECC过程中乌司他丁可以通过PMNE的释放从而减轻肺脏的缺血再灌注损伤,但是并没有起到抑制血小板激活的作用。

OBJECTIVE To investigate the influence of high-dose ulinastatin on cytokines and platelet activation during and after extracorporeal circulation（ECC）.METHODS 30 patients with coronary artery disease（CAD） undergoing coronary artery bypass graft（CABG） were randomly divided into two groups： U group（n=15） received a total dose of 1000000 U ulinastatin and C group（n=15） received placebo.Blood samples were withdrawn from the central vein to measure polymorphonuclear neutrophil elastase（PMNE）,before induction,30 min following clamping（T2）,reperfusion 3 h（T3）,reperfusion 6 h（T4） and reperfusion 12 h（T5）.Whole blood samples were taken for CD62p immediately before induction（as baseline）,at the end of ECC（before protamine administration）,1 h after heparin neutralization by protamine and 24 h after the operation. In addition,alveolo-arterial oxygen difference（A-aDO2） in pulmonary gas exchange function was calculated by obtaining arterial blood gas samples before and after ECC.RESULTS There were no differences in preoperative parameters between two groups.After ECC,the levels of PMNE increased in both groups over baseline values（P〈0.01）.The levels of PMNE,in U group were significantly lower than those in C group（P〈0.05）.No significant differences in CD62p expression between the 2 groups during ECC were found.AaDO2 in U group significantly decreased compared with C group（P〈0.05） and the duration of mechanical ventilation was shorter than C group（P〈0.05）.CONCLUSION Results suggest that ulinastatin may inhibit PMNE release,reduce reperfusion lung injury and preserve pulmonary function but it fails to inhibit platelet activation and to prevent blood loss during ECC.