Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis
Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis
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DOI：
10.1152/ajplung.1997.272.4.l720
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发表时间：
1997-04-01
影响因子：
4.9
通讯作者：
Ryan, RM
中科院分区：
文献类型：
--
作者：
DAngio, CT;Finkelstein, JN;Ryan, RM
肺损伤，包括支气管肺发育不良，会改变表面活性物质系统。为了研究肺表面活性物质蛋白(SP)基因的表达，我们建立了新生兔急性高氧性损伤模型。最初的窝暴露在>；95%O-2中，直到50%死亡(LD(50)；7-11日龄)。随后的窝仔暴露在95%O-2中8天，然后是60%O-2，直到22-36天。对照组暴露在室内空气中。LD(50)组动物表现为急性肺炎症、水肿、蛋白渗漏和肺表面活性物质功能障碍。这些变化消失了，22天后出现了纤维化。全肺SP-A基因表达(膜杂交法)在氧暴露4d时为对照水平的两倍，4d时在终末细支气管区和II型细胞中显著升高，原位杂交法在LD(50)处显著升高。在整个暴露过程中，全肺SP-B和SP-C的mRNA与对照组相比没有变化。然而，原位杂交显示LD(50)时炎症区II型细胞中SP-B和SP-C的mRNA表达升高。SP基因的改变在22-36天内消失。尽管持续60%的氧气暴露，表面活性物质系统仍能从急性高氧损伤中恢复。
Lung injuries, including bronchopulmonary dysplasia, alter the surfactant system. We developed a newborn rabbit model of acute, followed by chronic, hyperoxic injury to study surfactant protein (SP) gene expression. Initial litters were exposed to >95% O-2 until 50% died (LD(50); 7-11 days old). Subsequent litters were exposed to >95% O-2 for 8 days, followed by 60% O-2 until 22-36 days. Controls were exposed to room air. LD(50) animals displayed acute pulmonary inflammation, edema, protein leak, and surfactant dysfunction. These changes resolved, and fibrosis developed by 22 days. Whole lung SP-A mRNA expression (measured by membrane hybridization) was twice control levels at 4 days of >95% O-2, with specific elevations in terminal bronchioles and type II cells at 4 days and the LD(50) by in situ hybridization. Whole lung SP-B and SP-C mRNA were unchanged from control throughout exposure. However, in situ hybridization showed elevations in SP-B and SP-C mRNA in type II cells in inflamed areas at the LD(50). SP mRNA alterations resolved by 22-36 days. The surfactant system recovers from acute hyperoxic injury, despite continued 60% O-2 exposure.