Mild vitamin A deficiency delays fetal lung maturation in the rat
Mild vitamin A deficiency delays fetal lung maturation in the rat
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DOI：
10.1165/ajrcmb.21.1.3563
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发表时间：
1999-07-01
影响因子：
6.4
通讯作者：
Bourbon, JR
中科院分区：
文献类型：
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作者：
Chailley-Heu, B;Chelly, N;Bourbon, JR
在妊娠晚期，胎儿肺储存表面活性物质，为宫外生命做准备。表面活性物质缺乏，最常见的是由于早产，沉淀呼吸窘迫综合征（RDS）的新生儿。虽然维生素A（视黄醇）和视黄酸已被证明可以增强磷脂表面活性剂成分的合成，但它们对表面活性剂特异性蛋白质的影响尚不清楚。尚未尝试评估维生素A限制对表面活性剂磷脂储存或对生命必需的表面活性剂蛋白-B（SP-B）表达的影响。我们在大鼠中诱导部分维生素A缺乏症，导致血液视黄醇减少30-60%，这种状态与妊娠维持和后代无明显异常相一致。足月时，维生素A缺乏（VAD）胎儿的表面活性剂磷脂减少了21%，主要的表面活性剂磷脂，二饱和磷脂酰胆碱（DSPC）减少了27%。表面活性剂磷脂和DSPC的减少与血浆视黄醇呈线性相关，在视黄醇浓度最低的胎儿中达到约50%;它伴随着脂肪酸合成酶基因表达的减少，脂肪酸合成酶是表面活性剂磷脂脂质前体合成途径中的关键酶。在VAD胎儿中，SP-A、SP-B和SP-C信使RNA的量分别减少46%、32%和28%。同时，通过Western印迹法评估SP-A和SP-B蛋白的量减少。与对照肺相比，VAD中SP-B标记后确定的Ii型细胞的比例没有变化。因此，维生素A缺乏是肺成熟延迟的原因。鉴于其在人群中相当大的发病率，它可能代表RDS的风险增加和早产的加重因素。
During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, precipitates respiratory distress syndrome (RDS) of the neonate. Although vitamin A (retinol) and retinoic acid have been shown to enhance the synthesis of phospholipid surfactant components, their effect on surfactant-specific proteins is unclear. No attempt has been made to evaluate the consequences of vitamin A restriction on surfactant phospholipid storage or on the expression of the life-essential surfactant protein-B (SP-B). We induced in rats a partial vitamin A deficiency leading to a 30-60% reduction in blood retinol, a status compatible with maintenance of gestation and absence of gross abnormalities in offspring. At term, lang surfactant phospholipids were reduced by 21%, and the major surfactant phospholipid, disaturated phosphatidylcholine (DSPC), was reduced by 27% in vitamin A-deficient (VAD) fetuses. The decrease in surfactant phospholipids and DSPC correlated linearly with plasma retinol, and reached about 50% in fetuses with the lowest retinol concentrations; it was accompanied by reduced expression of the gene for fatty acid synthase, a key enzyme in the synthetic pathway for surfactant-phospholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consistently, amounts of SP-A and SP-B proteins were diminished as assessed by Western blotting. The proportion of type Ii cells determined after SP-B labeling was unchanged in VAD as compared with control lungs. Vitamin A deficiency is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk for RDS and an aggravating factor for prematurity.