胰岛素样生长因子结合蛋白-2与足月及早产新生大鼠高氧肺损伤的关系  

Relation of insulin-like growth factor binding protein-2 with hyperoxia-induced lung injury in term and premature neonatal rats

作　　者：刘汉楚[1] 常立文[1] 容志惠[1] 祝华平[1] 张谦慎[1] 陈红兵[1] 李文斌[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,湖北武汉430030

出　　处：《中国危重病急救医学》2008年第6期331-334,I0001,共5页Chinese Critical Care Medicine

基　　金：国家“十五”科技攻关计划资助项目（2004BA720A11）;国家自然科学基金资助项目（30471824）

摘　　要：目的探讨高浓度氧对足月及早产新生大鼠肺发育的影响及高氧肺损伤与胰岛素样生长因子结合蛋白-2（IGFBP-2）的关系。方法将孕22d自然出生（足月）及孕21d行剖宫术提前娩出（早产）的新生大鼠在生后2d随机分为足月空气组（Ⅰ组）、足月高氧组（Ⅱ组）、早产空气组（Ⅲ组）、早产高氧组（Ⅳ组）。Ⅱ、Ⅳ组持续暴露于氧含量为85％的氧箱中，Ⅰ、Ⅲ组置于同室空气中。每日记录大鼠存活率，分别于出生后4、7、10、14和21d活杀取肺组织标本，作病理学检查、辐射状肺泡计数（RAC）。用蛋白质免疫印迹法（Western blotting）及逆转录-聚合酶链反应（RT-PCR）分别测定IGFBP-2肺表达浓度及mRNA表达。结果高氧组自出生7d后大鼠存活率较空气组显著下降（P均〈0．01），但Ⅱ、Ⅳ组间差异无统计学意义（P〉0．05）。空气组肺组织无炎症病变；高氧组出生7d和14d时呈肺泡炎改变，21d时肺泡炎改变明显加重，且肺泡生成受阻滞，肺泡结构囊泡化；Ⅱ、Ⅳ组各时间点RAC值较相应Ⅰ、Ⅲ组显著减少（P均〈0．01）。高氧Ⅱ、Ⅳ组出生4d和14d IGFBP-2表达强度均较对应的Ⅰ、Ⅲ组增强（P均〈0．01）；IGFBP-2 mRNA表达变化与其肽浓度变化相似。结论长期高氧暴露可引起足月和早产新生大鼠亚急性肺损伤和肺发育阻滞，IGFBP-2异常表达；这可能是高氧导致亚急性肺损伤及肺发育阻滞的重要机制之一。Objective To study the deleterious effect of prolonged hyperoxic exposure on term and premature neonatal rat lungs and investigate the relationship between insulin-like growth factor binding protein （IGFBP）-2 and hyperoxia-induced lung injury in neonatal rats. Methods At the 22nd postnatal day Sprague-Dawley （SD） term-newborn or preterm-newborn rats were randomly divided into 4 groups, group Ⅰ： term-rats＋air group; group Ⅱ： term-rats＋hyperoxiagroup; group Ⅲ： preterm-rats＋air group; group Ⅳ： preterm-rats＋hyperoxia group. The rats in group Ⅱ and Ⅳ were exposed to about 85% （in volume） O2. The rats in group Ⅰ and Ⅱ were exposed to air in the same rooms. At 4, 7, 10, 14 and 21 days after birth, eight rats in each group were killed. The mortality of newborn rats was also recorded and lung radical alveolar counts （RAC） were examined. Lung histopathology with hematoxylin and eosin （HE） staining was examined ; The protein and mRNA of IGFBP-2 in the lung tissue were determined by Western blotting and by reverse transcription-polymerase chain reaction （RT-PCR）. Results After 7 days of 85% O2 exposure, the survival rate in group Ⅱ, Ⅳ were significant lower compared with group Ⅰ ,Ⅲ （all P〈0.01）, but no difference was found between group Ⅳ and group Ⅱ（P〈0.05）. No inflammatory change in lung tissue was found in group Ⅰ and Ⅲ. After 7 - 14 days of hyperoxia exposure, blood vessels in group Ⅱ , Ⅳ were dilated. Red blood cells and inflammatory cells were seen infiltrating into the alveolar space, and interstitium was thickened. After 21 days of hyperoxic exposure, inflammatory changes in group Ⅱ became more marked, and the alveolar walls or alveolar septa were markedly thickened. The formation of alveoli in group , Ⅳ was retarded and RACs at all time points were significantly lower than those in group Ⅰ ,Ⅲ（all P〈0.01）. After 4 days and 14 days, the expression of IGFBP-2 in the group Ⅱ and Ⅳ were significantly higher than th

关 键 词：胰岛素样生长因子结合蛋白-2 高氧 肺损伤 新生大鼠 

分 类 号：R722.6[医药卫生—儿科]