EFFECTS OF MATERNAL DIABETES MELLITUS ON THE FETAL LUNG

呼吸窘迫综合征(RDS)的发病率几乎呈上升趋势 糖尿病母亲(IDM)的婴儿，即使在适当的情况下，也是六倍 对胎龄进行了修正。IDMS出现高胰岛素血症 宫内和产后时期都是宫内的结果 高血糖，特别是当母亲的血糖平衡不佳时 控制住了。我们建议检验高胰岛素血症的假说 在体内，高血糖继发改变胎儿肺成熟 以及体外研究。体内研究：外源葡萄糖将被注入 进入慢性插管的胎羊，从那里可以得到气管积液 一直在收集。气管液的表面活性将是 在表面天平和表面活性剂浓度和通量上进行测定 气管积液将被量化。气管积液的脂类分析 将进行表面活性剂组成的圈定。 求出呼吸表面积和肺稳定指数 根据切除的肺的压力-容量曲线。胰岛素，皮质醇， β-交感神经，和甲状腺激素受体将在 全肺匀浆的胞核和胞浆部分。离体 研究：肺泡II型细胞(纯度大于95%)和肺 成纤维细胞(纯度大于95%)将从器官型分离出来 胎兔肺(孕26~31天)的培养及生长 用Warburton对道格拉斯和塞瓦尼安的改良进行单层培养 方法：研究方法。这些制剂将用于模拟和研究效果 IDM胎儿环境对肺细胞间相互作用的影响 实验分组：1.成纤维细胞条件培养液(FCM)的作用 由胰岛素、皮质醇、异丙肾上腺素和/或心得安和甲状腺制成 激素刺激的成纤维细胞生长(~3H胸腺嘧啶核苷DNA掺入)， 代谢率(14CO2产生)和表面活性物质合成和释放(3H 肺泡II型细胞的胆碱和~3H肌醇掺入 与直接处理的II型细胞比较。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的研究 肺泡II型细胞。3.肺对细胞外基质的提纯 成纤维细胞及其组成及其对肺泡II型细胞的影响 将对生长、代谢率和表面活性物质生产进行研究。在……里面 添加、修饰胰岛素产生的细胞外基质， 将对葡萄糖和皮质醇进行研究。

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.