Metyrapone Blocks Maternal Food Restriction-Induced Changes in Female Rat Offspring Lung Development
Metyrapone Blocks Maternal Food Restriction-Induced Changes in Female Rat Offspring Lung Development
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DOI：
10.1177/1933719113503404
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发表时间：
2014-04-01
影响因子：
2.9
通讯作者：
Torday, John S.
中科院分区：
文献类型：
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作者：
Rehan, Virender K.;Li, Yishi;Torday, John S.
妊娠期母体食物限制（MFR）通过未知机制影响宫内生长受限（IUGR）后代肺表面活性物质的产生。由于肺表面活性剂的产生受母体和胎儿皮质类固醇水平的调节，而在IUGR妊娠中，母体和胎儿的皮质类固醇水平都会升高，因此我们假设，糖皮质激素合成抑制剂metyrapone （MTP）会阻断MFR对后代表面活性剂产生的影响。采用三组孕鼠坝：(1)对照坝自由饲喂；(2)妊娠第10至22天的MFR（减少50%的卡路里）；(3)妊娠第11 ~ 22天，饮用水中MFR + MTP （0.5 mg/mL）。在5个月时，MFR后代的体重显著增加，肺泡数量减少，间隔厚度增加，表面活性剂蛋白和磷脂合成减少。这些MFR诱导的效应被抗糖皮质激素MTP正常化，这表明MFR应激导致了高皮质血症，改变了成年期的肺结构和功能。
Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood.