重组人促红细胞生成素对大鼠肝缺血再灌注诱发肺损伤的影响  

Effect of recombinant human erythropoietin on lung injury induced by hepatic ischemia-reperfusion in rats

作　　者：周荣胜[1] 朱慧慧[1] 刘庆波[1] 刘齐宁[1] 马正敏[1] 朱宇麟[1] 

机构地区：[1]西安交通大学医学院第一附属医院麻醉科,710061

出　　处：《中华麻醉学杂志》2015年第11期1385-1387,共3页Chinese Journal of Anesthesiology

基　　金：陕西省科技计划项目[2006K14-G2-（9）]

摘　　要：目的 评价重组人促红细胞生成素对大鼠肝缺血再灌注诱发肺损伤的影响.方法 健康雄性SD大鼠60只,6～8周龄,体重220～ 280 g,采用随机数字表法分为3组（n=20）：假手术组（S组）、肝缺血再灌注组（I/R组）和重组人促红细胞生成素组（E组）.I/R组和E组制备70％大部分肝缺血再灌注损伤模型.E组于造模前24 h时腹腔注射重组人促红细胞生成素4 000 U/kg,S组和I/R组腹腔注射等容量生理盐水.于再灌注3h时处死大鼠,取肺组织,HE染色后光镜下观察病理学结果,计算湿重/干重（W/D）比值;采用免疫组织化学法测定肺组织血红素氧合酶-1（HO-1）和诱导型一氧化氮合酶（iNOS）的表达,采用硫代巴比妥酸法测定丙二醛（MDA）含量,采用黄嘌呤氧化酶法测定超氧化物歧化酶（SOD）活性,采用氧化氢还原法测定髓过氧化物酶（MPO）活性.结果 与S组比较,E组和I/R组肺组织W/D比值、MDA含量及MPO活性升高,SOD活性降低,HO-1和iNOS表达上调（P＜0.05）,肺组织病理学损伤明显;与I/R组比较,E组肺组织W/D比值、MDA含量及MPO活性降低,SOD活性升高,HO-1表达上调,iNOS表达下调（P＜0.05）,肺组织病理学损伤减轻.结论 重组人促红细胞生成素可减轻大鼠肝缺血再灌注诱发肺损伤,其机制可能与上调肺组织HO-1的表达及下调iNOS的表达有关.Objective To evaluate the effect of recombinant human erythropoietin （rHuEPO） on lung injury induced by hepatic ischemia-reperfusion （I/R） in rats.Methods Sixty healthy male SpragueDawley rats, aged 6-8 weeks, weighing 220-280 g, were randomly divided into 3 groups （n=20 each） using a random number table： sham operation group （group S） , hepatic I/R group （group I/R）, and rHuEPO group （group E）.I/R and E groups underwent I/R of 70 percent of the liver.The rHuEPO 4 000 U/kg was injected intraperitoneally at 24 h before I/R in group E, while the equal volume of normal saline was given in S and I/R groups.The rats were sacrificed at 3 h of reperfusion, and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under light microscope.Wet to dry lung weight ratio （W/D ratio） was calculated.The expression of heme oxygenase-1 （HO-1） and inducible nitric oxide synthase （iNOS） in lung tissues was determined by immunohistochemistry.The content of malondialdehyde （MDA）, and activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） in lung tissues were detected.Results Compared with group S, the W/D ratio, MDA content, and MPO activity were significantly increased, the SOD activity was decreased, the expression of HO-1 and iNOS was up-regulated （P〈0.05） , and the pathological changes of lung tissues were obvious in E and I/R groups.Compared with group I/R, the W/D ratio, MDA content, and MPO activity were significantly decreased, the SOD activity was increased, the expression of HO-1 was up-regulated, the expression of iNOS was down-regulated （P〈0.05） , and the pathological changes of lung tissues were reduced in group E.Conclusion The rHuEPO can alleviate hepatic I/R-induced lung injury in rats, and the mechanism may be related to up-regulated expression of HO-1 and down-regulated expression of iNOS.

关 键 词：红细胞生成素 重组 再灌注损伤 肝 呼吸窘迫综合征 成人 

分 类 号：R575[医药卫生—消化系统]