CAJ | 학술논문

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22 d自然出生(足月)及孕21 d行剖宫术提前娩出(早产)的新生大鼠在生后2 d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21 d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7 d后大鼠存活率较空气组显著下降(P均<O.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7 d和14 d时呈肺泡炎改变,21 d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4 d和14 d 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.
목적 탐토고농도양대족월급조산신생대서폐발육적영향급고양폐손상여이도소양생장인자결합단백-2(IGFBP-2)적관계.방법 장잉22 d자연출생(족월)급잉21 d행부궁술제전면출(조산)적신생대서재생후2 d수궤분위족월공기조(I조)、족월고양조(Ⅱ조)、조산공기조(Ⅲ조)、조산고양조(Ⅳ조).Ⅱ、Ⅳ조지속폭로우양함량위85%적양상중,I、Ⅲ조치우동실공기중.매일기록대서존활솔,분별우출생후4、7、10、14화21 d활살취폐조직표본,작병이학검사、복사상폐포계수(RAC).용단백질면역인적법(Western blotting)급역전록-취합매련반응(RT-PCR)분별측정IGFBP-2폐표체농도급mRNA표체.결과 고양조자출생7 d후대서존활솔교공기조현저하강(P균<O.01),단Ⅱ、Ⅳ조간차이무통계학의의(P>0.05).공기조폐조직무염증병변;고양조출생7 d화14 d시정폐포염개변,21 d시폐포염개변명현가중,차폐포생성수조체,폐포결구낭포화;Ⅱ、Ⅳ조각시간점RAC치교상응I、Ⅲ조현저감소(P균<0.01).고양Ⅱ、Ⅳ조출생4 d화14 d IGFBP-2표체강도균교대응적I、Ⅲ조증강(P균<0.01);IGFBP-2 mRNA표체변화여기태농도변화상사.결론 장기고양폭로가인기족월화조산신생대서아급성폐손상화폐발육조체,IGFBP-2이상표체;저가능시고양도치아급성폐손상급폐발육조체적중요궤제지일.
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+hyperoxia group;group Ⅲ:preterm-rats+air group;group Ⅳ:preterm-rats+hyperoxia group.The rats in group Ⅱand Ⅳ were exposed to about 85% (in volume) O2.The rats in group I and Ⅲ 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>O.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 Ⅱ,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 those in group Ⅰ,Ⅲ (all P<0.01).The expression of mRNA of IGFBP-2 showed the same tendency of the protein in all 4 groups.Conclusion The prolonged exposure to hyperoxia may cause subacute lung injury and the retardation of lung development in term-neonatal or preterm-neonatal rats.The abnormal expressions of 1GFBP-2 correlate with hyperoxia-induced lung injury in neonatal rats.