Lucey E C, Goldstein R H, Stone P J, Snider G L
Boston VA Medical Center and the Pulmonary Center and Biochemistry Department, Boston University School of Medicine, Boston, Massachusetts, USA.
Am J Respir Crit Care Med. 1998 Aug;158(2):555-64. doi: 10.1164/ajrccm.158.2.9705021.
Treatment of hamster lungs with porcine pancreatic elastase (PPE) causes emphysema and a decrease in lung elastin content, which returns to control level by Day 30. To explore the mechanism of alveolar wall remodeling after elastolytic injury, we examined the expression of elastin and alpha1(I) collagen mRNAs by in situ hybridization at 1, 2, 3, 5, 7, and 30 d after intratracheal PPE. The lungs of control animals displayed weak signals for elastin and alpha1(I) collagen mRNA in pleura, large arteries, veins, and airways. There was little or no signal in respiratory air space walls. Increased expression of elastin and alpha1(I) collagen mRNA began by Day 1 after PPE and reached an asymptote by Day 3 that was maintained by elastin until Day 7; expression of alpha1(I) collagen mRNA waned earlier. Elastin and, to a lesser extent, alpha1(I) collagen mRNA were heavily expressed in pleura, blood vessels, and airways. Analysis of serial sections showed elastin message was minimal in the walls of respiratory air spaces and when present, at 3, 5, and 7 d, was primarily found at the free margins of alveolar septa. Collagen message was very sparse in respiratory air space walls. By 30 d, elastin mRNA expression was reduced but still above control levels and emphysema was widespread and severe. Rank score of elastin mRNA expression in individual subpleural air spaces showed a positive correlation with air space size. In conclusion, most expression of elastin and alpha1(I) collagen mRNA occurs in the pleura, airway, and vascular walls. In respiratory air space walls, expression of elastin mRNAs occurs in damaged tissue at free septal margins.
用猪胰弹性蛋白酶（PPE）处理仓鼠肺会导致肺气肿和肺弹性蛋白含量降低，到第30天时恢复至对照水平。为探究弹性蛋白酶损伤后肺泡壁重塑的机制，我们在气管内注入PPE后的第1、2、3、5、7和30天，通过原位杂交检测弹性蛋白和α1（I）型胶原mRNA的表达。对照动物的肺在胸膜、大动脉、静脉和气道中显示出较弱的弹性蛋白和α1（I）型胶原mRNA信号。呼吸性气腔壁中几乎没有信号。PPE处理后第1天开始，弹性蛋白和α1（I）型胶原mRNA的表达增加，到第3天达到平台期，弹性蛋白的表达一直维持到第7天；α1（I）型胶原mRNA的表达下降得更早。弹性蛋白以及程度较轻的α1（I）型胶原mRNA在胸膜、血管和气道中大量表达。连续切片分析显示，呼吸性气腔壁中的弹性蛋白信号极少，在第3、5和7天时，若有信号，主要出现在肺泡间隔的游离边缘。胶原信号在呼吸性气腔壁中非常稀少。到第30天时，弹性蛋白mRNA表达降低，但仍高于对照水平，且肺气肿广泛而严重。单个胸膜下气腔中弹性蛋白mRNA表达的秩评分与气腔大小呈正相关。总之，弹性蛋白和α1（I）型胶原mRNA的大部分表达发生在胸膜、气道和血管壁中。在呼吸性气腔壁中，弹性蛋白mRNA的表达发生在受损组织的间隔游离边缘。
