FETAL LUNG MATURATION: PREVENTION OF RDS

胎儿肺成熟：RDS 的预防

• 批准号: 3096746
• 负责人: JOHN M JOHNSTON
• 金额: $ 54.29万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3096746
• 关键词: embryo /fetus; histogenesis; human fetus tissue; lung; pulmonary surfactants; respiratory distress syndrome of newborn

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.

本课题提出的研究对象 (续签)拨款申请是为了定义分子事件 与胎儿II型肺泡巨噬细胞的差异有关 从而为防治该病提供了合理的依据。 呼吸窘迫综合征(RDS)。项目1的目标是 明确糖原代谢与糖原代谢的关系 表面活性剂甘油磷脂的合成。双环芳香烃的合成 血小板活化因子及其在糖原分解中的作用将是 调查过了。胞苷电荷和表面活性剂的作用 表面活性物质甘油磷脂调节中的载脂蛋白 将对新陈代谢进行研究。管理的机制 表面活性物质甘油磷脂的可能调节酶 合成将被确定。项目2的目标是定义 调节发育的分子机制 主要表面活性物质载脂蛋白编码基因的表达 (SP-35)及其激素调节。的变化 该基因在胎肺发育过程中的转录活性 以及激素对mRNAs合成和半抑制的影响。 生活将被评估。参与发育的基因组区域 和SP-35基因的激素调节将被识别和 与这些区域相互作用的DNA结合蛋白将是 与世隔绝的，有特点的。SP-35基因将在大肠杆菌中表达 真核细胞了解更多关于它的功能。目标是 项目3的目的是确定肾上腺素能系统在 发育中的胎儿肺。阿尔法和贝塔激动剂的作用， 环磷酸腺苷类似物和磷酸二酯酶抑制剂的水平 对SP-35及其mRNA的表达进行了定义。各种不同因素的影响 激素对胎肺组织环磷酸腺苷水平的影响 下定决心。对照和处理的胎肺外植体将 通过光学显微镜和电子显微镜进行评价。表面活性剂 将对肺中的载脂蛋白和甘油磷脂进行定量 低出生体重儿的灌洗液 茶碱。项目4的目标是定义开发 Low的表达及免疫细胞化学定位 胎儿中疏水表面活性物质载脂蛋白的相对分子质量 阿龙。胰岛素等调节因子对其影响的研究 将评估胎儿肺组织中的合成和积累。 胰岛素对胎肺的形态影响将是 描述。表面活性物质脱辅基蛋白的浓度 糖尿病患者和非糖尿病患者的羊水标本 怀孕的情况将会确定。项目5的目标是 确定延长宫内“应激”的机制 改变慢性仪器化胎儿的胎肺成熟 怀孕的绵羊。雌二醇-17β、精氨酸的作用 加压素、利托定以及长期胎盘低灌注症 血浆应激激素和气管液水平的研究 将在最后30天内对表面活性剂成分进行评估 我的胃口。我们将在以下地点采集脐带血样本 胎儿过长的风险人类妊娠所生的时间 “压力”并将压力荷尔蒙的变化与 RDS的发生情况。包含28,000对母婴和 出生体重小于1500克的1,400名婴儿将被用于 确定有长期宫内应激的婴儿是否有 肺功能改变。