Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development
Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development
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DOI：
10.1152/ajplung.2000.279.6.l1159
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发表时间：
2000-12-01
影响因子：
4.9
通讯作者：
Shannon, JM
中科院分区：
文献类型：
--
作者：
Guilbert, TW;Gebb, SA;Shannon, JM
致畸剂除草醚在啮齿动物胎儿中产生先天性腹股沟疝（CDH）和肺发育不全，这与在人类中观察到的结果非常相似。我们推测这些变化可能是由于原发性肺发育不全而不是腹腔内容物疝出所致。定时妊娠大鼠在第9天给予除草醚，并在第13天至第21天收获胎儿。在除草醚处理的胎儿中，妊娠第11天肺芽的初始外翻没有延迟。然而，在妊娠第13天，与对照组相比，暴露于除草醚的胎儿肺部末端芽的数量显著减少。胸苷标记的肺上皮细胞和间充质细胞显着减少，在除草醚处理的肺。除草醚处理胎仔的肺表现出宽隔膜，组织紊乱，致密，特别是在气隙周围。表面活性蛋白B和C mRNA的表达显着降低除草醚窝。在所有胎龄的胎儿肺组织原位杂交显示血管内皮生长因子，Flk-1，或Flt-1 mRNA的表达没有差异。由于大鼠在妊娠第16天完成横膈膜闭合，我们的研究结果表明，该CDH模型中的肺发育不全至少部分是由于除草醚对发育中的肺的主要影响。
The teratogen nitrofen produces a congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia in rodent fetuses that closely parallel observations made in humans. We hypothesized that these changes may be due to primary pulmonary hypoplasia and not herniation of the abdominal contents. Timed-pregnant rats were given nitrofen on day 9, and fetuses were harvested on days 13 through 21. Initial evagination of lung buds on gestational day 11 was not delayed in nitrofen-treated fetuses. On gestational day 13, however, there was a significant decrease in the number of terminal end buds in the lungs of nitrofen-exposed fetuses vs. controls. Thymidine-labeled lung epithelial and mesenchymal cells were significantly decreased in nitrofen-treated lungs. Lungs from nitrofen-treated fetuses exhibited wide septae with disorganized, compacted tissue, particularly around the air spaces. Expression of surfactant protein B and C mRNAs was significantly decreased in the nitrofen litters. In situ hybridization of fetal lung tissue at all gestational ages showed no difference in the expression of vascular endothelial growth factor, Flk-1, or Flt-1 mRNAs. Because closure of the diaphragm is completed on gestational day 16 in the rat, our results suggest that lung hypoplasia in this model of CDH is due at least in part to a primary effect of nitrofen on the developing lung.