乌司他丁后处理及其联合预处理对体外循环下心脏瓣膜置换术患者心肌细胞凋亡的影响  

Effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass

作　　者：王焰斌 杨建安 景桂霞[3] 王小雷 黄志勇 翟宇佳 程毅坚 杨晓涵 李刚 王湘 

机构地区：[1]孙逸仙心血管医院麻醉科,广东省深圳市518020 [2]孙逸仙心血管医院心脏外科,广东省深圳市518020 [3]西安交通大学第一附属医院麻醉科

出　　处：《中华麻醉学杂志》2011年第9期1068-1072,共5页Chinese Journal of Anesthesiology

基　　金：2010年深圳市科技计划项目（201002118）;2010年天普研究基金（01200903）

摘　　要：目的评价乌司他丁后处理及其联合预处理对CPB下心脏瓣膜置换术患者心肌细胞凋亡的影响。方法择期CPB下心脏瓣膜置换术患者80例，性别不限，年龄21～59岁，心功能分级Ⅱ或Ⅲ级。采用随机数字表法，将患者随机分为4组（n=20）：生理盐水对照组（C组）、乌司他丁预处理组（U1组）、乌司他丁后处理组（U2组）和乌司他丁预处理联合后处理组（U3组）。U1组进行乌司他丁预处理：于气管插管后～升主动脉阻断前10min经中心静脉输注乌司他丁500—1000U·kg-1·min-1（剂量20000U／kg），U2组进行乌司他丁后处理：于主动脉开放前5～7min经主动脉根部灌注乌司他丁4000-5000U·kg-1·min-1（剂量10000U／kg），U组进行乌司他丁预处理联合后处理，c组给予等容量生理盐水。分别于升主动脉阻断前10min、升主动脉阻断后40min、升主动脉开放后45min和术毕时采集动脉血样，分离血浆，测定血浆肿瘤坏死因子-α（TNF-α）和可溶性肿瘤坏死因子受体1（sTNF-R1）浓度。于升主动脉开放后45min时取右心耳心肌组织，测定TNF-α、Bcl-2、Bαx、cαspαse-3表达和细胞凋亡情况，并计算Bcl-2与Bαx的比值（Bcl-2／Bαx比率）和凋亡指数（AI）。结果与C组比较，U1组、U2组和U3组血浆TNF．α和sTNF—R1的浓度及AI降低，心肌组织TNF—α、Bαx、cαspαse-3表达下调，Bcl-2表达上调，Bcl-2／Bαx比率升高（P〈O．05）；与u。组和U2组比较，U3组血浆TNF-α和sTNF—R1的浓度和AI降低，心肌组织TNF-α、Bαx和cαspαse-3表达下调，Bcl-2表达上调，Bcl-2／Bαx比率升高（P〈0．05）。结论乌司他丁后处理可抑制CPB下心脏瓣膜置换术患者心肌细胞凋亡，联合预处理时其效应增强，其机制与平衡心肌细胞Bcl-2与Bx表达及下调TNF—α及其受体表达有关。Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass （CPB）.Methods Eighty NYHA class Ⅱ or Ⅲ patients of both sexes, aged 21-59, scheduled for cardiac valve replacement with CPB, were randomly divided into 4 groups （ n = 20 each） ： normal saline control group （ group C ）, ulinastatin preconditioning group （ group U1）, ulinastatin postconditioning group （group U2 ） and ulinastatin preconditioning plus postconditioning group（group U3 ）. In group U1 ,uinastatin 20 000 U/kg was infused via central vein at 500-1000 U·kg-1·min-1 from after tracheal intubation until 10 min before ascending aortic cross-clamping. In group U2, ulinastatin 10 000 U/kg was perfused via aortic root at 4000-5000 U·kg-1·min-1 at 5-7 min before aortic unclamping. In group U3, ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2. In group C same volume normal saline was infused instead of ulinastatin. Blood samples were taken from radial artery at 10 min before ascending aortic cross-clamping, 40 min after ascending aortic cross-clamping,45 min after aortic unclamping and the end of operation for determination of plasma concentrations of TNF-a and soluble tumor necrosis factor receptor 1 （sTNF-Rt）. Myocardial tissues were obtained from right atrial appendage at 45 min after aortic unclamping for determination the expression of TNF-α, Bcl-2, Bax and caspase-3 and apoptosis. The Bcl-2/Bax ratio and apoptotic index were calculated. Results Plasma concentrations of TNF-a and sTNF-R~ and the expression of TNF-α, Bax, caspase-3 and apoptotic index were lower,the expression of Bel-2 and Bcl-2/Bax ratio were higher in groups Ul ,U2 and U3 than group C and in group U3 than groups U1, U2 （ P 〈 0.05）. Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients under

关 键 词：胰蛋白酶抑制剂 心肌再灌注损伤 细胞凋亡 缺血预处理 心肌 心肺转流术 心脏瓣膜假体植入 后处理 

分 类 号：R654.2[医药卫生—外科学]