乌司他丁对急性肝功能衰竭大鼠肝组织中血红素加氧酶-1mRNA和蛋白表达的影响  

Effect of ulinastatin on mRNA and protein expressions of hemeoxygenase-1 in liver tissue of acute liver failure rats

作　　者：谷甸娜[1] 陈永平[1] 张晓华[1] 卢洁[1] 张磊[1] 郑毅[1] 郑明华[1] 

机构地区：[1]温州医学院附属第一医院感染内科,325000

出　　处：《中华传染病杂志》2009年第4期207-211,共5页Chinese Journal of Infectious Diseases

基　　金：基金项目：浙江省科技厅新苗人才计划项目（2007R40G2090032）;浙江省卫生厅项目（20078141）

摘　　要：目的探讨乌司他丁对急性肝功能衰竭的保护作用及对血红素加氧酶-1（hemeoxygenase-1，HO-1）的影响。方法66只S—D大鼠分为对照组、模型组和乌司他丁干预组，通过腹腔注射D-氨基半乳糖（D-Gal）及脂多糖（LPS）建立大鼠急性肝功能衰竭模型，动态观察（6、12、24、36和48h）大鼠血清ALT、AST和丙二醛（MDA）含量变化，RT-PCR检测肝脏HO-1mRNA变化，免疫组织化学方法检测HO-1蛋白表达。多组间差异比较采用单因素方差分析，两两比较采用LSD法。结果D-Gal／LPS联合注射成功诱导大鼠急性肝功能衰竭模型，表现为造模6h后血清ALT、AST水平以及肝组织MDA浓度均显著升高（F值分别为23．864、38．446、18．051，均P〈0．01），以12至24h之间最为显著。造模24h后，模型组与干预组ALT、AST、MDA分别达到（8346．7±1363．1）U／L、（9766．7±1274．1）U／L、（8．34±1．13）umol／g与（4151.3±970．0）U／L、（4696．7±1476．9）U／L、（4．66±0．91）μmol／g，均较对照组的（24．0±2．0）U／L、（82．3±16．9）U／L、（2．55±0．22）μmol／g高（F值分别为55．684、55．501、47．843，均P〈0．01），但干预组显著低于模型组（P〈0．01）；与对照组相比，模型组HO-1mRNA及其蛋白表达增加（P〈0．01），干预组的上升更加显著（P〈O．01）。结论乌司他丁能上调HO-1mRNA和蛋白表达，提示乌司他丁可能通过HO-1通路发挥其在急性肝功能衰竭中抗炎抗氧化的保护作用。Objective To study the protective role of ulinastatin in acute liver failure （ALF） and the effect on the expression of hemeoxygenase-1 （HO-1）. Methods Sixty-six S-D rats were divided into three groups： control group, ALF group （model group） and ulinastatin group （intervention group）. The rat model of ALF was induced by intraperitoneal injection of D-galactosamine （D-GaD and lipopolysaccharide （LPS）. The serum levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and malondialdehyde （MDA） were detected dynamically after 6, 12, 24, 36 and 48 h injection. HO-1 mRNA expression in liver tissue was determined by reverse transcriptionpolymerase chain reaction （RT-PCR）, and the expression of HO-1 protein was detected by immunohistochemistry. The differences among multiple groups were compared by univariate ANOVA and pairwise comparison was done by least significant difference （LSD）. Results D-Gal/LPS injections successfully induced ALF rat model which presented with elevated levels of serum ALT, AST and liver MDA after 6 h injections （F： 23. 864, 38. 446, 18. 051, respectively, all P〈0.01）,and peaked at 12--24 h after injections. Twenty-four hours after D-Gal/LPS treatment, the levels of serum ALT, AST and MDA in model group and intervention group were （8 346.7±1 363.1） U/L vs （4 151.3±970.0） U/L, （9 766. 7±1 274. 1） U/L vs （4 696. 7±1 476. 9） U/L, （8.34±1. 13） μmol/g vs （4.66±0.91） μmol/g, respectively, which were significantly higher than those [（24.0± 2.0） U/L, （82.3±16.9） U/L, （2.55±0.22） μmol/g, respectively, in control group （F=55. 684, 55. 501, 47. 843, respectively, all P〈0.01） ; while those in intervention group were much lower than those in model group （P〈0.01）. The expressions of HO-1 mRNA and protein in model group were significantly increased than those in control group （P〈0. 01）, while those in intervention group were even higher （P〈0.01）. Conclusion Ulinastain cou

关 键 词：胰蛋白酶抑制剂 血红素氧化酶(脱环) 肝功能衰竭 急性 RNA 信使 大鼠 

分 类 号：R575.3[医药卫生—消化系统] R383.24[医药卫生—内科学]