Prenatal treatment with retinoic acid promotes pulmonary alveologenesis in the nitrofen model of congenital diaphragmatic hernia
Prenatal treatment with retinoic acid promotes pulmonary alveologenesis in the nitrofen model of congenital diaphragmatic hernia
复制标题
DOI：
10.1016/j.jpedsurg.2007.10.030
复制
发表时间：
2008-03-01
影响因子：
2.4
通讯作者：
Puri, Prem
中科院分区：
文献类型：
--
作者：
Montedonico, Sandra;Sugimoto, Kaoru;Puri, Prem
背景/目的：严重的肺发育不良仍然是新生儿先天性膈疝（CDH）死亡率高的主要原因。类维生素A是维生素A衍生的分子家族，其在肺发育中起重要作用。我们假设，维甲酸促进肺泡形成在妊娠结束，因此设计了这项研究，探讨维甲酸对除草醚诱导的肺发育不良在CDH.Methods：怀孕的大鼠暴露于橄榄油或100毫克除草醚在妊娠第9天的影响。在妊娠第18、19和20天腹腔内给予视黄酸5 mg/kg，并在第21天回收胎仔。我们有4个研究组：对照组（n = 24）、对照+维甲酸组（n = 22）、CDH组（n = 24）和CDH +维甲酸组（n = 19）。固定4个研究组的肺，并在垂直随机切片上进行以下体视学测量：肺总体积、气隙体积密度、气壁体积密度、气体交换表面积、肺泡体积和每个肺的肺泡总数。用分光光度计测定各肺的总DNA含量。结果：CDH肺的总肺体积增加后，视黄酸，但在对照组保持不变。添加维甲酸后，CDH肺的气体交换表面积较大，但对照组无变化。加入维甲酸后，每个肺的肺泡总数更高。总DNA含量以及总DNA含量肺重量比的左肺CDH组中增加显着后，添加维甲酸与CDH没有维甲酸acid.Conclusions：我们的研究结果表明，产前治疗与维甲酸刺激肺泡发育不良的肺CDH。(C)2008年爱思唯尔公司All rights reserved.
Background/Purpose: Severe pulmonary hypoplasia remains the main cause of the high mortality in newborn infants with congenital diaphragmatic hernia (CDH). Retinoids are a family of molecules derived from vitamin A, which play an important role in lung development. We hypothesized that retinoids promote alveologenesis at the end of gestation and therefore designed this study to investigate the effects of retinoid acid on nitrofen-induced hypoplastic lungs in CDH.Methods: Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation. Retinoic acid 5 mg/kg was given intraperitoneally on days 18, 19, and 20 of gestation and fetuses were recovered on day 21. We had 4 study groups: control (n = 24), control + retinoic acid (n = 22), CDH (n = 24), and CDH + retinoic acid (n = 19). Lungs from the 4 study groups were fixed, and the following stereological measurements were performed on vertical random sections: total lung volume, volume density of airspaces, volume density of air walls, gas exchange surface area, alveolar volume, and total number of alveoli per lung. Total DNA content of each lung was measured using a spectrophotometer.Results: Total lung volume increased in CDH lungs after the addition of retinoic acid but remained the same in the control group. Gas exchange surface area was larger in CDH lungs after the addition of retinoic acid but remained unchanged in the control group. The total number of alveoli per lung was higher after the addition of retinoic acid. Total DNA content as well as total DNA content-lung weight ratio of the left lung increased significantly in the CDH group after the addition of retinoic acid compared with CDH without retinoic acid.Conclusions: Our results demonstrate that prenatal treatment with retinoic acid stimulates alveologenesis in hypoplastic lungs in CDH. (C) 2008 Elsevier Inc. All rights reserved.