FETAL LUNG MATURATION: PREVENTION OF RDS

胎儿肺成熟：RDS 的预防

• 批准号: 3096750
• 负责人: JOHN M JOHNSTON
• 金额: $ 40.76万
• 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/3096750
• 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.

我们建议阐明胎儿肺中的分子事件，这些事件涉及 二棕榈酰磷脂酰胆碱（DP-PC）的生物合成， 磷脂酰甘油（PG）。 磷脂酸磷酸水解酶（PAPase）的作用， 胆碱磷酸转移酶和CTP：磷酸胆碱胞苷酰转移酶 胞苷一磷酸（CMP）形成的调控及其机制 将棕榈酸盐富集磷脂酰胆碱（PC）以形成DP-PC， 研究了 我们设想，胎肺中CMP水平可能调节 磷脂酰肌醇（PI）和PG的形成。CMP的可用性增加 导致CMP形成胞苷二磷酸甘油二酯（CDP-DG）增加 和PI，导致磷脂酰甘油磷酸（PGP）形成增加。 我们 认为PAPase催化磷脂酸转化为 sn-1，2-甘油二酯和PGP转化为PG。 II型肺细胞中的PAPase活性在肺纤维化中是非常重要的。 合成的PC，PI，和PG。参与的SER，高尔基体， 将研究板层体形成中的溶酶体。 的作用 雌激素、皮质醇、胰岛素和催乳素在 II型肺细胞和参与雌激素和 催乳素受体将受到特别关注。 板层的释放 将研究来自II型肺细胞的体。 体内的荷尔蒙变化 将通过测定与肺成熟有关人类胎儿的肺成熟度来研究 脐带血催乳素、皮质醇、 雌激素与L/S比值和RDS发生率的关系。 我们特别感兴趣 在评估可能经历过的新生儿的激素环境时， 胎儿，加速或延迟肺成熟，并确定如何产妇 并发症可能会改变胎儿的激素环境和时间表， 胎肺成熟 这些研究的结果将是基本的， 了解肺成熟的生物化学基础， 制定合理的治疗模式以加速肺成熟 在人类胎儿中。