McGillick Erin V, Morrison Janna L, McMillen I Caroline, Orgeig Sandra
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and Molecular and Evolutionary Physiology of the Lung Laboratory, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and.
Am J Physiol Regul Integr Comp Physiol. 2014 Sep 1;307(5):R538-45. doi: 10.1152/ajpregu.00053.2014. Epub 2014 Jul 2.
Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein (SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.
循环中胎儿葡萄糖和胰岛素浓度升高是胎儿肺成熟的潜在抑制剂，可能与糖尿病母亲婴儿呼吸窘迫综合征（RDS）的发病机制有关。在本研究中，我们研究了向妊娠晚期绵羊胎儿体内输注葡萄糖对肺中葡萄糖转运蛋白、胰岛素样生长因子信号、糖皮质激素调节基因和表面活性物质蛋白mRNA表达的影响。使用免疫组织化学方法测定负责产生表面活性物质的细胞的数值密度。输注葡萄糖10天未影响葡萄糖转运蛋白或胰岛素样生长因子的mRNA表达，但降低了IGF-1R的表达。糖皮质激素转化酶HSD11B-1和糖皮质激素受体的mRNA表达降低，可能会降低胎儿肺对糖皮质激素的反应性。此外，输注葡萄糖后肺中表面活性物质蛋白（SFTP）的mRNA表达降低，而SFTP-B阳性细胞数量保持不变。这些发现表明存在一种糖皮质激素介导的机制，调节绵羊胎儿输注葡萄糖后表面活性物质系统的延迟成熟，并为孕期血糖控制异常与未控制糖尿病母亲婴儿患RDS风险增加之间的联系提供了证据。
