血红素加氧酶-1表达对大鼠呼吸机相关性肺损伤的作用及机制研究  

A study of the role of heme oxygenase-1 expression in ventilator induced lung injury and its mechanism in rats

作　　者：赵文静[1] 胡伟伟[1] 

机构地区：[1]江苏省麻醉与镇痛应用技术实验室、徐州医学院麻醉学院,221002

出　　处：《中国危重病急救医学》2010年第7期410-413,I0002,共5页Chinese Critical Care Medicine

基　　金：江苏省科技厅社会发展基金（2005019）;江苏省“六大人才高峰”第六批资助项目（卫生行业200938）

摘　　要：目的 观察呼吸机相关性肺损伤（VILI）模型大鼠肺组织中血红素加氧酶-1（HO-1）表达的变化,探讨HO-1诱导剂血晶素拮抗VILI的作用机制.方法 56只雄性SD大鼠按照随机数字表法分成对照组（C组）,VILI模型组（M组）,诱导剂血晶素1、2、3、4组（H1、 H2、H3、H4组,制模前24 h分别腹腔注射血晶素40、80、120、160 μmol/kg）和抑制剂Z组[制模前24 h腹腔注射锌原卟啉（ZnPP）10 μmol/kg].除C组外各组机械通气4 h后处死大鼠,收集支气管肺泡灌洗液（BALF）,测定总蛋白、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）含量;取肺组织,测定肺湿/干重（W/D）比值、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）和丙二醛（MDA）水平及HO-1蛋白表达;光镜下行肺组织病理观察.结果 与C组相比,M组大鼠肺病理损伤严重,BALF中总蛋白、TNF-α、IL-10,肺组织W/D比值、MDA、LDH及HO-1蛋白表达均明显增加, VILI模型复制成功.与M组比较,随着血晶素剂量的增加,H1、H2、H3组总蛋白（g/L）显著下降（0.74±0.06、0.73±0.07、0.70±0.07比0.84±0.08,均P〈0.01）;W/D比值下降（4.93±0.27、4.91±0.24、4.87±0.23比5.53±0.48,均P〈0.01）;SOD活性（U/mg）显著升高（85±9、82±15、93±11比55±12,均P〈0.01）;MDA含量（nmol/mg）显著降低（15±3、15±3、13±2比18±4,P〈0.05或P〈0.01）;IL-10含量（pg/L）逐渐升高（0.42±0.06、0.46±0.06、0.47±0.05比0.36±0.07）,TNF-α含量（pg/L）逐渐降低（0.18±0.07、0.14±0.03、0.10±0.07比0.23±0.06）,但只有H2、H3组差异有统计学意义（均P〈0.01）;LDH活性（U/g）降低（11 353±1 317、11 516±1 613、9 631±1 520比12 361±1 841）,但仅H3组差异有统计学意义（P〈0.01）;HO-1蛋白表达[吸光度（A）值]逐渐增强（0.164±0.010、0.190±0.149、0.205±0.018比0.122±0.016,均P〈0.01）;肺病理损伤逐渐减轻.而随着剂量进一步增加,H4组肺组织损伤较H1、H2、H3组加重.�Objective To observe the changes in heme oxygenase-1 （HO-1） expression in lung tissue with ventilator induced lung injury （VILI） in rats, and to explore the mechanism of preventive effect of HO-1 inducer hemin on VILI. Methods Fifty-six male Sprague-Dawley （SD） rats were randomly divided into control group （group C）, VILI model group （group M）, hemin group 1, 2, 3, 4 （group H1, H2, H3, H4, with intraperitoneal injection of hemin 40, 80, 120, 160 μmol/kg, respectively, 24 hours before model was reproduced）, and suppressor Z group （intraperitoneal injection of ZnPP 10 μmol/kg 24 hours before reproduction of the model）. After 4 hours of ventilation, all rats, except those of group C, were sacrificed, and bronchoalveolar lavage fluid （BALF） was collected. Total protein, the contents of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） in BALF were measured. The lung tissue specimen was collected, the wet-to-dry weight ratio （W/D）, the level of lactate dehydrogenase （LDH）, superoxide dismutase （SOD）, malondialdehyde （MDA） and HO-1 protein expression were determined. Lung pathological changes were observed with microscope. Results In group M, rat lung tissue was seriously damaged, and total protein in BALF, TNF-α, IL-10, W/D of lung, MDA and LDH activity, as well as HO-1 protein expression were markly higher than those in group C, denoting that VILI model was successfully reproduced. Compared with group M, the total protein in BALF （g/L） in group H1, H2, H3 was gradually reduced （0.74±0.06, 0.73±0.07, 0.70±0.07 vs. 0.84±0.08, all P〈0.01） with an increase in hemin dose. W/D of lung was reduced （4.93±0.27, 4.91±0.24, 4.87±0.23 vs. 5.53±0.48, all P〈0.01）. The activity of SOD （U/mg） was higher （85±9, 82±15, 93±11 vs. 55±12, all P〈0.01）, and the content of MDA （nmol/mg） was decreased （15±3, 15±3, 13±2 vs. 18±4, P〈0.05 or P〈0.01）. The content of IL-10 （pg/L） in BALF was higher （0.42±0.06, 0.46±0

关 键 词：血晶素 呼吸机相关性肺损伤 血红素加氧酶-1 抗炎症作用 抗氧化应激 

分 类 号：R563[医药卫生—呼吸系统]