Warburton D
J Clin Invest. 1983 Aug;72(2):433-40. doi: 10.1172/jci110991.
I tested the hypothesis that chronic hyperglycemia with secondary hyperinsulinemia inhibits the stimulation of fetal lung maturation by cortisol. Glucose was infused (16 +/- 2 mg/kg per min, mean +/- SE) from 112 through 130 d gestation into five chronically catheterised twin fetal lambs from which tracheal fluid could be collected. In addition, cortisol was infused (420 micrograms/h) from 128 through 130 d gestation into both the five glucose-treated twins and the five twin controls. Serum glucose (48 +/- 2 mg/dl) and insulin levels (45 +/- 3 microU/ml) were significantly higher in the glucose-treated fetuses than serum glucose (23 +/- 2 mg/dl, P less than 0.001) and insulin (15 +/- 3 microU/ml, P less than 0.001) in the controls. Serum cortisol levels were less than 2 micrograms/dl before 128 d gestation and rose to greater than 6 micrograms/dl, P less than 0.001 during cortisol infusion in both the glucose-treated and control fetuses. Cortisol treatment of control fetuses was associated with a 4.8-fold increase in surface active material (SAM) flux into tracheal fluid, and a 7.7-fold increase in total phospholipid content, a 9.5-fold increase in mixed lecithin content, a 10.5-fold increase in disaturated phosphatidylcholine content, and a 5.6-fold increase in phosphatidylglycerol content of the tracheal fluid (all P less than 0.001). In the glucose-treated fetuses there were no significant changes in the tracheal fluid SAM flux and phospholipid content following cortisol administration. In lung wash from the control fetuses treated with cortisol there was 8.9-fold more SAM, and on thin-layer chromatography there was 5.6-fold more total phospholipids, 3.9-fold more mixed lecithin, 6.2-fold more disaturated phosphatidylcholine, and 2.5-fold more phosphatidylglycerol when compared with lung wash from the glucose-treated fetuses treated with cortisol (all P less than 0.001). Lung volumes at maximal inflation pressure during air pressure-volume studies were 1.8-fold greater in the cortisol-treated control fetuses than in the glucose-treated fetuses, P less than 0.025. Chronic hyperglycemia with secondary hyperinsulinemia inhibits the maturational response of fetal lamb lungs to cortisol. A similar mechanism may operate in utero to increase the incidence of respiratory distress syndrome in infants of diabetic mothers with poor maternal glucose homeostasis. Moreover, on the basis of these data, prenatal treatment of infants of diabetic mothers with corticosteroids might not be expected to enhance fetal lung maturation.
伴有继发性高胰岛素血症的慢性高血糖会抑制皮质醇对胎儿肺成熟的刺激作用。在妊娠112至130天期间，对5只长期插管的双胎胎儿羔羊输注葡萄糖（16±2毫克/千克每分钟，均值±标准误），这些羔羊的气管液可以收集。此外，在妊娠128至130天期间，对5只接受葡萄糖治疗的双胎羔羊和5只双胎对照羔羊均输注皮质醇（420微克/小时）。接受葡萄糖治疗的胎儿的血清葡萄糖（48±2毫克/分升）和胰岛素水平（45±3微单位/毫升）显著高于对照组的血清葡萄糖（23±2毫克/分升，P<0.001）和胰岛素（15±3微单位/毫升，P<0.001）。妊娠128天前，两组胎儿的血清皮质醇水平均低于2微克/分升，在接受皮质醇输注期间，两组胎儿的血清皮质醇水平均升至大于6微克/分升，P<0.001。对对照胎儿进行皮质醇治疗后，气管液中表面活性物质（SAM）通量增加4.8倍，总磷脂含量增加7.7倍，混合卵磷脂含量增加9.5倍，二饱和磷脂酰胆碱含量增加10.5倍，气管液中磷脂酰甘油含量增加5.6倍（所有P<0.001）。在接受葡萄糖治疗的胎儿中，给予皮质醇后气管液SAM通量和磷脂含量无显著变化。与接受皮质醇治疗的葡萄糖处理胎儿的肺灌洗相比，接受皮质醇治疗的对照胎儿的肺灌洗中SAM多8.9倍，在薄层色谱上总磷脂多5.6倍，混合卵磷脂多3.9倍，二饱和磷脂酰胆碱多6.2倍，磷脂酰甘油多2.5倍（所有P<0.001）。在气压-容积研究中，最大充气压力下的肺容积，接受皮质醇治疗的对照胎儿比接受葡萄糖治疗的胎儿大1.8倍，P<0.025。伴有继发性高胰岛素血症的慢性高血糖会抑制胎儿羔羊肺对皮质醇的成熟反应。类似的机制可能在子宫内起作用，增加患有糖尿病且母体葡萄糖稳态不良的母亲所生婴儿呼吸窘迫综合征的发生率。此外，基于这些数据，可能无法预期对患有糖尿病的母亲所生婴儿进行产前皮质类固醇治疗会促进胎儿肺成熟。
