乌司他丁预先给药对肝切除术大鼠氧化应激反应和肝细胞生长因子的影响  

Effects of ulinastatin pretreatment on oxidative stress response and hepatocyte growth factor after hepatectomy in rats

作　　者：朱宇麟[1] 赵鸽[1] 刘齐宁[1] 周荣胜[1] 张晓琪[1] 吕毅[2] 

机构地区：[1]西安交通大学医学院第一附属医院麻醉科,710061 [2]西安交通大学医学院第一附属医院肝胆外科,710061

出　　处：《中华麻醉学杂志》2012年第9期1136-1139,共4页Chinese Journal of Anesthesiology

基　　金：天普研究基金（012009040）

摘　　要：目的探讨乌司他丁预先给药对肝切除术大鼠氧化应激反应和肝细胞生长因子（HGF）的影响。方法健康清洁级雄性sD大鼠112只，体重230—280g，3月龄，采用随机数字表法，将大鼠随机分为2组（n=56）：肝切除术组（H组）和乌司他丁预先给药组（u组）。2组切除肝左叶和中叶并阻断肝右叶和尾叶的血流进行缺血，30min时恢复灌注，u组于缺血前5min静脉注射乌司他丁50000U／kg。每组分别于缺血前、再灌注1、6、12、24和48h时取8只大鼠，采集下腔静脉血样，测定血清ALT、AST和HGF水平，然后取肝右叶组织，测定肝细胞凋亡指数（AI）、SOD和髓过氧化物酶（MPO）活性、MDA含量、增殖细胞核抗原表达，计算肝再生度。每组取8只大鼠，记录术后7d内生存情况。结果与H组比较，u组各时点AIJT及AST活性、AI、髓过氧化物酶活性和MDA含量降低，HGF浓度、SOD活性、增殖细胞核抗原表达和肝再生度升高（P〈0．05），术后7d内生存率差异无统计学意义（P〉0．05）。结论乌司他丁预先给药可增强肝切除术大鼠肝再生功能，其机制与抑制氧化应激反应和促进HGF生成有关。Objective To investigate the effects of ulinastatin pretreatment on oxidative stress response and hepatocyte growth factor （HGF） after hepatectomy in rats. Methods One hundred and twelve pathogen-free male Sprague-Dawley rats, aged 3 months, weighing 230-280 g, were randomly divided into 2 groups （ n = 56 each）： group hepatectomy （group H） and group ulinastatin pretreatment （group U）. Left and median lobe resec- tion was perfommd and then liver ischemia was induced by blood flow occlusion of right and caudate lobes for 30 min, followed by perfusion in both groups. Ulinastatin 50 000 U/kg was injected intravenously at 5 min before oc- clusion in group U. Eight rats in each group were chosen and the blood samples were taken from the inferior vena cavafor t of serum ALT and AST activities and HGF concentration before ischemia and at 1, 6, 12, 24 and 48 h of reperfusion. Then the right lobe were removed for determination of apoptosis, SOD and myeloperoxi- dase （MPO） activities, MDA content, expression of proliferating cell nuclear antigen （PCNA） and liver regenera- tion. Apoptotic index was calculated. Another 8 rats in each group were chosen and the 7 day survival rate was recorded. Results Compared with group H, the levels of ALT, AST, MPO and MDA and apoptotic index were significantly decreased, and the levels of HGF and SOD, PCNA expression and liver regeneration were significantly increased at different time points in group U （ P 〈 0.05）. There was no significant difference in 7 day survival rate between group H and group U （ P 〉 0.05）. Conclusion Ulinastatin pretreatment can strengthen liver regeneration after hepatectomy in rats, the underlying mechanism may be related to inhibition of oxidative stress response and increase in HGF production.

关 键 词：胰蛋白酶抑制剂 肝切除术 氧化性应激 肝细胞生长因子 

分 类 号：R614[医药卫生—麻醉学]