Dekowski S A, Snyder J M
Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242, USA.
Pediatr Res. 1995 Oct;38(4):513-21. doi: 10.1203/00006450-199510000-00007.
Infants of diabetic mothers are frequently hyperinsulinemic and have an increased incidence of neonatal respiratory distress syndrome, a disease caused by a deficiency in the production of pulmonary surfactant by alveolar type II cells. It has been hypothesized that insulin inhibits fetal lung type II cell differentiation. We have shown previously that insulin inhibits the accumulation of surfactant protein (SP)-A and SP-B mRNA and has no effect on SP-C mRNA levels in human fetal lung tissue maintained in vitro. We hypothesized that treatment with glucocorticoids, which are used clinically to accelerate human fetal lung maturation, would overcome the inhibitory effects of insulin on human fetal lung development. In the present study, human fetal lung explants were maintained in the presence or absence of cortisol added alone, or in insulin plus cortisol added together. Cortisol significantly decreased SP-A mRNA levels by approximately 50% at the 100 nM concentration and significantly increased levels by approximately 20% at the 1 nM concentration. Cortisol increased SP-B and SP-C mRNA levels in a dose-dependent fashion (5- and 45-fold at 100 nM cortisol, respectively). The combination of 1 nM cortisol and insulin resulted in inhibition of mRNA levels for SP-A, SP-B, and SP-C at the high insulin concentrations (approximately 50% inhibition for SP-A and SP-B and approximately 25% inhibition of SP-C mRNA levels, in the presence of 40 pmol/L x 10(-3) insulin). Surprisingly, 100 nM cortisol plus inhibitory concentrations of insulin increased SP-A mRNA levels (2-fold at 40 pmol/L x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)
患有糖尿病母亲的婴儿常出现高胰岛素血症，且新生儿呼吸窘迫综合征的发病率增加，该疾病是由肺泡II型细胞产生肺表面活性物质不足所致。据推测，胰岛素会抑制胎儿肺II型细胞分化。我们之前已经表明，胰岛素会抑制表面活性蛋白（SP）-A和SP-B mRNA的积累，而对体外培养的人胎儿肺组织中SP-C mRNA水平没有影响。我们推测，临床上用于加速人胎儿肺成熟的糖皮质激素治疗，将克服胰岛素对人胎儿肺发育的抑制作用。在本研究中，人胎儿肺外植体在单独添加皮质醇或同时添加胰岛素和皮质醇的情况下进行培养。皮质醇在100 nM浓度时可使SP-A mRNA水平显著降低约50%，在1 nM浓度时可使水平显著升高约20%。皮质醇以剂量依赖方式增加SP-B和SP-C mRNA水平（在100 nM皮质醇时分别增加5倍和45倍）。1 nM皮质醇和胰岛素的组合在高胰岛素浓度下导致SP-A、SP-B和SP-C的mRNA水平受到抑制（在存在40 pmol/L×10(-3)胰岛素的情况下，SP-A和SP-B约受50%抑制，SP-C mRNA水平约受25%抑制）。令人惊讶的是，100 nM皮质醇加上抑制浓度的胰岛素会增加SP-A mRNA水平（在40 pmol/L×10(-3)时增加2倍）。（摘要截断于250字）
