高氧诱导肺损伤新生鼠肺表面活性蛋白基因表达的研究

The expression of surfactant protein genes hyperoxia-induced neonatal rat lung injury

目的:探讨高氧对肺组织结构和表面活性蛋白(Surfactant protein,SP)A、B、C、D(SP-A、SP-B、SP-C、SP-D)基因表达的影响和机制。方法:应用高氧诱导新生大鼠肺损伤观察肺组织结构和SP-A、SP-B、SP-C、SP-D基因表达的变化。将生后6h内的SD新生大鼠随机分为空气组和高氧组,于1、4、7d和14d4个时间点,分别取肺组织,计算肺系数(肺重/体重×100%),通过HE染色观察组织病理学变化,采用逆转录-聚合酶链反应(Reverse transcription-polymerase chain reaction,RT-PCR)检测SP mRNAs的表达。结果:高氧组14d新生大鼠体重低于空气组,差异有显著统计学意义(P<0.01),而7d和14d新生大鼠的肺系数明显高于空气组相应时间点,差异有显著统计学意义(P<0.05);高氧组1、4d和7d新生大鼠SP-A、SP-D mRNAs的表达均高于空气组相应时间点,且差异有显著统计学意义(P<0.05),14d新生大鼠的表达水平较空气组减低,差异有显著统计学意义(P<0.05);高氧组1、4d新生大鼠SP-B、SP-C mRNAs的表达均高于空气组,且差异有显著统计学意义(P<0.05),7d差异无显著统计学意义(P>0.05),而14d新生大鼠的表达水平较空气组减弱,差异有显著统计学意义(P<0.05)。结论:长期高氧抑制肺泡发育,并抑制肺SP基因的表达,这可能是肺损伤的重要因素。

Objective：To observe the effects of hyperoxiaon the changes of pulmonary histology and surfactant protein gene expression.Methods：SD newborns which less than 6 h old were randomly divided into 2 groups：normal air control group and hyperoxia group.The lungs of rats were removed at the time points 1,4,7,14 d,histopathological changes of the lung tissues were examined by HE staining and the lung factor were calculated（lung weight/body weight ×100%）;the expression of all surfactant protein genes were detected by semi-quantitative reverse transcription-polymerase chain reaction（RT-PCR）.Results：To compare with corresponding air control group,in hyperoxia group,the body weight is significantly deceased after 14 days of hyperoxia exposure（P〈0.01）,and the lung factor increased significantly from day 7（P〈0.05）,and kept increasing at 14 d（P〈0.05）;the levels of SP-A and SP-D mRNAs increased significantlyfromday1（P〈0.05）,remained higher at 4 d and 7 d（P〈0.05）,and began tosignificantlydecreased at 14 d（P〈0.05）;the levels of SP-B and SP-C mRNAs increased from day 1（P〈0.05）,remained higher at 4 d（P〈0.05）,but there were no significant differences at 7 d（P〉0.05）,and began to significantly decreased at 14 d（P〈0.05）.Conclusion：Prolonged hyperoxia can inhibit the development of alveolar and the expression of surfactant protein genes indicating that alterations in gene expression,contribute to tissue injury.