FETAL LUNG MATURATION: PREVENTION OF RDS

本项目拟研究的对象 （更新）补助金申请是为了定义分子事件 参与胎儿II型肺细胞的差异， 从而为治疗和预防 呼吸窘迫综合征（RDS）。 项目1的目标是 确定糖原代谢与 表面活性剂甘油磷脂合成 的合成 血小板活化因子及其在糖原分解中的作用将是 研究了 胞苷酸电荷和表面活性剂的作用 载脂蛋白在调节表面活性剂甘油磷脂中的作用 将研究代谢。 管理的机制 表面活性剂甘油磷脂的推定调节酶 将确定合成。 项目2的目标是定义 介导发育的分子机制 主要表面活性物质脱辅基蛋白基因的表达 （SP-35）及其激素调节。 变化 胎儿肺发育过程中基因的转录活性 以及激素对mRNA合成和半- 生命将被评估。 参与发育的基因组区域 和SP-35基因的激素调节将被确定， 与这些区域相互作用的DNA结合蛋白将被 分离并表征。 SP-35 cDNA将在 真核细胞来了解更多关于它的功能。 目标 项目3的目的是确定肾上腺素能系统在 发育中的胎儿肺 α和β激动剂的作用， 环AMP类似物和磷酸二酯酶抑制剂的水平 SP-35及其mRNA的表达。 反应的影响 激素对胎儿肺组织环磷酸腺苷水平的影响将是 测定 将对照和处理的胎仔肺外植体 通过光学和电子显微镜进行评价。 表面活性 将定量肺中的载脂蛋白和甘油磷脂 从低出生体重婴儿获得的灌洗液， 茶碱 项目4的目标是确定发展 表达和免疫细胞化学定位 分子量，胎儿疏水表面活性剂载脂蛋白 肺。 胰岛素和其他调节因素对他们的影响 将评估胎儿肺组织中的合成和积累。 胰岛素对胎肺的形态学影响将是 介绍了 表面活性剂脱辅基蛋白的浓度 从糖尿病患者和非糖尿病患者中获得的羊水 怀孕将被确定。 项目5的目标是 确定长期的子宫内“压力” 在长期使用仪器的胎儿中改变胎肺成熟， 怀孕的羊 雌二醇-17 β，精氨酸 垂体后叶素、利托定以及持续性胎盘低灌注 对血浆应激激素和气管液的影响 将在最后30天内对表面活性剂成分进行评价， gastation。 我们会在下列地点抽取脐带血样本： 从人类怀孕的出生时间延长的风险feta “压力”和相关的变化，压力荷尔蒙与 RDS的发生。 28 000对母婴的数据库， 1,400名出生体重低于1500克的婴儿将被用于 确定长期宫内应激的婴儿是否 肺功能改变

The object of the research proposed in this Program Project (Renewal) Grant Application is to define the molecular events involved in the differences of fetal type II pneumonocytes and thus provide a rational basis for the treatment and prevention of respiratory distress syndrome (RDS). The goal of Project 1 is to define the relationship between glycogen metabolism and the synthesis of surfactant glycerophospholipids. The synthesis of platelet-activating factor and its role in glycogenolysis will be investigated. The role of the cytidylate charge and surfactant apoproteins in the regulation of surfactant glycerophospholipid metabolism will be investigated. The mechanisms that govern the putative regulatory enzymes of surfactant glycerophospholipid synthesis will be determined. The goal of Project 2 is to define the molecular mechanisms that mediate the developmental expression of the gene encoding the major surfactant apoprotein (SP-35) and the hormonal regulation thereof. Changes in the transcriptional activity of the gene during fetal lung development as well as the effect of hormones on mRNAs synthesis and half- life will be evaluated. Genomic regions involved in developmental and hormonal regulation of the SP-35 gene will be identified and DNA binding proteins that interact with these regions will be isolated and characterized. The SP-35 cDNA will be expressed in eukaryotic cells to learn more concerning its function. The goal of Project 3 is to determine the role of the adrenergic system in developing fetal lung. The effects of alpha and beta agonists, cyclic AMP analogs, and phosphodiesterase inhibitors on the levels of SP-35 and its mRNA will be defined. The effects of various hormones on cyclic AMP levels in fetal lung tissue will be determined. Control and treated fetal lung explants will be evaluated by light and electron microscopy. Surfactant apoproteins and glycerophospholipids will be quantitated in lung lavage obtained from low birth weight infants treated with theophylline. The goal of Project 4 is to define the developmental expression and immunocytochemical localization of the low molecular weight, hydrophobic surfactant apoproteins in fetal lung. The effects of insulin and other regulatory factors on their synthesis and accumulation in fetal lung tissue will be evaluated. The morphological effects of insulin on fetal lung will be described. The concentration of surfactant apoproteins in amniotic fluids obtained from diabetic and nondiabetic pregnancies will be determined. The goal of Project 5 is to determine the mechanism whereby prolonged intrauterine "stress" alters fetal lung maturation in chronically instrumented fetal and pregnant sheep. The effects of estradiol-17 beta, arginine vasopressin, ritodine as well as prolonged placental hypoperfusion on the plasma levels of stress hormones and tracheal fluid surfactant components will be evaluated during the last 30 days of gastation. We will obtain umbilical cord blood samples at the time of birth from human pregnancies at risk of prolonged feta "stress" and correlate changes in stress hormones with the occurrance of RDS. Databases of 28,000 mother-infant pairs and 1,400 infants, is less than 1500 gm birth weight, will be utilized to determine whether infants with prolonged intrauterine stress have altered pulmonary function.