EFFECTS OF MATERNAL DIABETES MELLITUS ON THE FETAL LUNG

呼吸窘迫综合征（RDS）的发病率几乎 糖尿病母亲（IDM）的婴儿，即使在适当的情况下， 对胎龄进行校正。 糖尿病女性出现高胰岛素血症 无论是在子宫内和产后时期，由于子宫内 高血糖症，特别是当母体葡萄糖稳态差时 控制。 我们建议检验高胰岛素血症 继发于高血糖改变胎儿肺成熟， 和体外研究。 体内研究：将输注外源性葡萄糖 注入长期插管的胎羊体内， 不断收集。 气管液的表面活性将 在表面平衡和表面活性剂浓度和通量上测定， 将对气管液体进行定量。 气管液脂质分析 将进行，以描绘表面活性剂的组成。 计算呼吸表面积和肺稳定性指数 从切除的肺的压力-容积曲线。 胰岛素，皮质醇， β-拟交感神经和甲状腺激素受体将在 全肺匀浆的细胞核和细胞质部分。 体外 研究：肺泡II型细胞（纯度大于95%）和肺 将成纤维细胞（纯度大于95%）从器官型成纤维细胞中分离出来。 培养胎兔肺（妊娠26-31天），并在 采用沃伯顿改良的道格拉斯和塞瓦尼安单层培养法 方法. 这些制剂将用于模拟和研究 IDM的胎儿环境对肺细胞之间的相互作用在三个 实验分组：1. 成纤维细胞条件培养基（FCM）的作用 用胰岛素、皮质醇、异舒普林和/或普萘洛尔和甲状腺素制备 激素暴露的成纤维细胞对生长的影响（3 H胸苷DNA掺入）， 代谢率（14 CO2产生）和表面活性剂合成和释放（3 H 胆碱和3 H肌醇掺入）的肺泡II型细胞， 与直接处理的II型细胞相比。 2. 上述FCM的影响 皮质醇，胰岛素，β-交感神经和甲状腺激素受体， 肺泡II型细胞 3. 细胞外基质经肺释放 成纤维细胞、其组成及其对肺泡II型细胞的作用 将研究生长、代谢率和表面活性剂产生。 在 此外，通过胰岛素修饰细胞外基质的产生， 将研究葡萄糖和皮质醇。

The incidence of respiratory distress syndrome (RDS) is increased almost sixfold in infants of diabetic mothers (IDM), even when suitable corrections are made for gestational age. IDMs experience hyperinsulinemia both in utero and in the postnatal period as a result of intrauterine hyperglycemia, particularly when maternal glucose homeostasis is poorly controlled. We propose to examine the hypothesis that hyperinsulinemia secondary to hyperglycemia alters fetal lung maturation using both in vivo and in vitro studies. In vivo studies: Exogenous glucose will be infused into chronically catheterised fetal lambs from which tracheal fluid can be continuously collected. Surface activity of the tracheal fluid will be assayed on a surface balance and surfactant concentration and flux in tracheal fluid will be quantified. Lipid analysis of the tracheal fluid will be carried out in order to delineate surfactant composition. Respiratory surface area and the stability index of lungs will be derived from pressure-volume curves of excised lungs. Insulin, cortisol, beta-sympathomimetic, and thyroid hormone receptors will be assayed in nuclear and cytoplasmic fractions of whole lung homogenates. In vitro studies: Alveolar type II cells (greater than 95% purity) and lung fibroblasts (greater than 95% purity) will be separated from organotypic cultures of fetal rabbit lungs (26-31 days gestation) and grown in monolayer culture using Warburton's modification of Douglas' and Sevanian's methods. These preparations will be used to simulate and study the effects of the IDM's fetal environment on interactions between lung cells in three groups of experiments: 1. Effects of fibroblast conditioned media (FCM) prepared with insulin, cortisol, isoxuprine and/or propranolol, and thyroid hormone exposed fibroblasts on growth (3H thymidine DNA incorporation), metabolic rate (14CO2 production) and surfactant synthesis and release (3H choline and 3H myo-inositol incorporation) by alveolar type II cells in comparison with directly treated type II cells. 2. Effects of above FCM on cortisol, insulin, beta-sympathominetic and thyroid hormone receptors in alveolar type II cells. 3. Elaboration of extracellular matrix by lung fibroblasts, its composition and its effects on alveolar type II cell growth, metabolic rate and surfactant production will be studied. In addition, modification of extracellular matrix production by insulin, glucose and cortisol will be studied.