权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

FETAL LUNG MATURATION: PREVENTION OF RDS

胎儿肺成熟：RDS 的预防

基本信息

批准号：
3096754
负责人：
JOHN M JOHNSTON
金额：
$ 69.39万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-05-01 至 1993-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3096754
关键词：
embryo /fetus histogenesis low birth weight infant human lung pulmonary surfactants respiratory distress syndrome of newborn

项目摘要

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.

本计划项目提出的研究对象（续订）资助申请是为了定义分子事件涉及胎儿II型肺细胞的差异从而为治疗和预防提供合理依据呼吸窘迫综合征（RDS）。项目 1 的目标是定义糖原代谢与糖原代谢之间的关系表面活性剂甘油磷脂的合成。的合成血小板活化因子及其在糖原分解中的作用调查了。胞苷酸电荷和表面活性剂的作用脱辅基蛋白对表面活性剂甘油磷脂的调节将研究新陈代谢。治理机制表面活性剂甘油磷脂的推定调节酶合成将被确定。项目 2 的目标是定义介导发育的分子机制编码主要表面活性剂脱辅基蛋白的基因的表达 (SP-35)及其激素调节。的变化胎儿肺发育过程中基因的转录活性以及激素对 mRNA 合成和半合成的影响人生将会受到评价。参与发育的基因组区域 SP-35 基因的激素调节将被确定与这些区域相互作用的 DNA 结合蛋白将分离并表征。 SP-35 cDNA 将在真核细胞以了解更多有关其功能的信息。目标项目 3 的目的是确定肾上腺素能系统在正在发育的胎儿肺。 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 的定义将被定义。各种效果激素对胎儿肺组织中环磷酸腺苷水平的影响决定。对照和处理过的胎儿肺外植体将通过光学和电子显微镜进行评估。表面活性剂将对肺中的脱辅基蛋白和甘油磷脂进行定量从接受过治疗的低出生体重婴儿获得的灌洗液茶碱。项目 4 的目标是定义发展低表达和免疫细胞化学定位胎儿中的分子量、疏水性表面活性剂脱辅基蛋白肺。胰岛素和其他调节因素对其的影响将评估胎儿肺组织中的合成和积累。胰岛素对胎儿肺的形态学影响描述的。表面活性剂脱辅基蛋白的浓度来自糖尿病和非糖尿病患者的羊水将确定怀孕。项目 5 的目标是确定长期宫内“应激”的机制改变长期接受仪器治疗的胎儿的胎儿肺成熟度怀孕的羊。雌二醇-17β、精氨酸的作用加压素、利托定以及长时间胎盘低灌注对应激激素和气管液血浆水平的影响表面活性剂成分将在最后 30 天内进行评估胃气。我们将在以下地点获取脐带血样本：存在羊胎时间延长风险的人类妊娠的出生时间 “压力”并将压力荷尔蒙的变化与 RDS 的发生。包含 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患有肺功能改变。