FETAL LUNG MATURATION: PREVENTION OF RDS

胎儿肺成熟：RDS 的预防

• 批准号: 3096749
• 负责人: JOHN M JOHNSTON
• 金额: $ 38.23万
• 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 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3096749
• 关键词: embryo /fetus; histogenesis; lung; pulmonary surfactants; respiratory distress syndrome of newborn

We propose to elucidate the molecular events in fetal lung which are involved in the biosynthesis of dipalmitoylphosphatidylcholine (DP-PC) and phosphatidylglycerol (PG). The role of phosphatidate phosphohydrolase (PAPase), cholinephosphotransferase, and CTP:phosphocholine cytidylyl transferase in the regulation of cytidine monophosphate (CMP) formation and the mechanisms for palmitate enrichment of phosphatidylcholine (PC) to form DP-PC will be investigated. We envision that CMP levels in the fetal lung may regulate the formation of phosphatidylinositol (PI) and PG. Increased availability of CMP leads to increased cytidine diphosphate diglyceride (CDP-DG) formation from CMP and PI, leading to increased phosphatidylglycerolphosphate (PGP) formation. We believe that PAPase catalyzes both the conversion of phosphatidic acid to sn-1,2-diglycerides and of PGP to PG. Hence, the mechanism controlling the activity of PAPase in the type II pneumocyte is of major importance in the synthesis of PC, PI, and PG. The participation of the SER, Golgi apparatus, and lysosomes in lamellar body formation will be investigated. The role of estrogen, cortisol, insulin, and prolactin in the biochemical maturation of the type II pneumocyte and the events involved in the expression of estrogen and prolactin receptors will be given special attention. The release of lamellar bodies from the type II pneumocyte will be studied. The hormonal events in the human fetus which are related to lung maturation will be studied by determining the relationship of umbilical cord plasma levels of prolactin, cortisol, and estrogen to the L/S ratio, and incidence of RDS. We are especially interested in evaluating the hormonal milieu of newborns who may have experienced, as fetuses, accelerated or delayed lung maturation and to ascertain how maternal complications may alter the hormonal milieu of the fetus and the timetable of fetal lung maturation. The findings of such studies will be fundamental to the understanding of the biochemical basis of lung maturation and are essential to the formulation of a rational treatment paradigm to accelerate lung maturation in human fetuses.

我们建议阐明胎肺中涉及的分子事件。 二棕榈酰磷脂酰胆碱(DP-PC)和 磷脂酰甘油(PG)。磷脂酸盐磷酸水解酶(PAPase)的作用 胆碱磷酸转移酶和CTP：磷酸胆碱胞苷转移酶 胞苷一磷酸(CMP)形成的调控及其机制 棕榈酸酯浓缩磷脂酰胆碱(PC)形成DP-PC将 调查过了。我们设想，胎肺中的cMP水平可能调节 磷脂酰肌醇(PI)和PG的形成。提高了CMP的可用性 导致CMP形成胞二磷二甘油酯(CDP-DG)的增加 和PI，导致磷脂酰甘油磷酸(PGP)的形成增加。我们 相信PAPase催化磷脂酸转化为 SN-1，2-二甘油三酯和PGP为PG。因此，控制这一现象的机制 肺泡II型细胞中PAPase活性在肺泡灌洗液中起重要作用 PC、PI和PG的合成。SER、高尔基仪器和 将对板层小体形成过程中的溶酶体进行研究。的作用 雌激素、皮质醇、胰岛素和催乳素在卵巢细胞生化成熟中的作用 II型肺泡细胞及其参与雌激素和雌激素表达的事件 催乳素受体将受到特别关注。片剂的释放 将对来自II型肺细胞的身体进行研究。人类的荷尔蒙事件 人类胎儿与肺成熟有关的研究将通过确定 脐血浆催乳素、皮质醇水平与妊娠结局的关系 雌激素对L/S比值、RDS发生率的影响。我们特别感兴趣的是 在评估新生儿的荷尔蒙环境时，他们可能经历了 胎儿，肺成熟加速或延迟，并确定母体 并发症可能会改变胎儿的荷尔蒙环境和 胎儿肺发育成熟。这些研究的结果将是 了解肺成熟的生化基础，对于 制定促进肺成熟的合理治疗方案 在人类胎儿身上。