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Hypoxia Effects on Amniotic Fluid Volume

缺氧对羊水量的影响

基本信息

批准号：
7494994
负责人：
ROBERT A BRACE
金额：
$ 32.2万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-10 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7494994
关键词：
Accounting Albumins Amniotic Fluid Bicarbonates Biochemical Biological Transport Blood Circulation Blood Vessels Body Temperature Braces-Orthopedic appliances CAV1 gene Caveolae Cells Cessation of life Characteristics Chorion Clinical Compatible Complex Condition Data Diffusion Electron Microscopy Endothelial Cells Exhibits Fetal Death Fetal Diseases Fetal Membranes Fetus Gases Gene Expression Glucose Goals Hypoxia In Vitro Individual Insufflation Inulin Ions Knowledge Label Lead Liquid substance Localized Measures Mediating Membrane Messenger RNA Methodology Methods Microscopy Minor Modeling Molecular Neonatal Nitrogen Numbers Oligohydramnios Oxygen Oxygen measurement, partial pressure, arterial Pathway interactions Physiological Placenta Placental Insufficiency Play Polyhydramnios Polyuria Potassium Chloride Pregnancy Premature Birth Production Property Proteins Publishing Radio Radioactive Tracers Rate Regulation Relative (related person)Research Design Respiratory distress Role Saline Series Sheep Side Sodium Structural Protein Surface Technetium Temperature Therapeutic Embolization Tissues Tracer Trachea Transfusion Transport Process Transport Vesicles Urea Vascular Endothelial Growth Factor Receptor Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Vesicle Water absorption amnion base caveolin 1 cell type fetal fetal blood fetus hypoxia improved in utero in vivo insight macromolecule mortality neonatal morbidity passive transport protein expression radius bone structure response size small molecule solute

项目摘要

DESCRIPTION (provided by applicant): Recent studies have shown that amniotic fluid (AF) volume is regulated by modulating the rate of intramembranous absorption and that vascular endothelial growth factor (VEGF) may play a pivotal role in this regulation. This absorption occurs against hydrostatic, concentration and experimentally induced osmotic gradients. However, the mechanisms mediating intramembranous transport as well as the regulation of intramembmnous absorption are unknown. The proposed studies utilize chronically catheterized fetal sheep to characterize intramembranous transport mechanisms and determine the underlying cellular and molecular regulation during normoxia and during 3 forms of fetal hypoxia which individually produce increased, unchanged, or reduced AF volume. We will determine the contribution of diffusion versus bulk transport to intramembranous absorption of water and solutes. These interpretations will be confirmed by measuring the intramembranous unidirectional fluxes of specific solutes in the AF to fetal and fetal to AF directions. The cellular and molecular mechanisms which regulate passive and bulk transfer through the intramembranous pathway will be determined by studying the effects of VEGF on transport in isolated amniotic membrane and amnion cells in culture. Our overall hypothesis is that intramembranous bulk flow occurs by unidirectional vesicular transport; that hypoxia augments bulk flow but not passive diffusion; and that the rate of vesicular transport is determined by the abundance and mobility of vesicles in the amnion. We further hypothesize that hypoxia augments VEGF expression which in turn regulates caveolin-1 expression and/or increases vesicle abundance and mobility. The proposed studies are important because oligohydramnios is a frequent clinical problem associated with fetal hypoxia accounting for many in utero fetal deaths due to cord compression and neonatal deaths due to respiratory distress. Polyhydramnios is associated with premature delivery and fetal diseases including anemic hypoxia. The proposed studies will lead to a dramatic improvement in our understanding of AF volume regulation under normal as well as hypoxic conditions. This knowledge will promote a rational basis for improved therapies to treat AF volume abnormalities, thereby helping to reduce fetal and neonatal morbidity and mortality.

描述（申请人提供）：最近的研究表明，羊水（AF）量是通过调节膜内吸收速率来调节的，而血管内皮生长因子（VEGF）可能在这种调节中发挥着关键作用。这种吸收是在静水压、浓度和实验诱导的渗透梯度的作用下发生的。然而，介导膜内运输以及膜内吸收调节的机制尚不清楚。拟议的研究利用长期插管的胎羊来表征膜内转运机制，并确定常氧期间和三种形式的胎儿缺氧期间的潜在细胞和分子调节，这三种形式分别产生增加、不变或减少的 AF 体积。我们将确定扩散与散装运输对膜内水和溶质吸收的贡献。这些解释将通过测量 AF 到胎儿以及胎儿到 AF 方向上特定溶质的膜内单向通量来证实。通过研究 VEGF 对培养的分离羊膜和羊膜细胞转运的影响，将确定通过膜内途径调节被动和大量转运的细胞和分子机制。我们的总体假设是膜内整体流动是通过单向囊泡运输发生的；缺氧会增加总体流量，但不会增加被动扩散；囊泡运输的速率由羊膜中囊泡的丰度和活动性决定。我们进一步假设缺氧会增强 VEGF 表达，进而调节 Caveolin-1 表达和/或增加囊泡丰度和活动性。拟议的研究很重要，因为羊水过少是与胎儿缺氧相关的常见临床问题，导致许多胎儿因脐带受压而死亡，以及新生儿因呼吸窘迫而死亡。羊水过多与早产和胎儿疾病（包括贫血缺氧）有关。拟议的研究将极大地提高我们对正常和缺氧条件下房颤容量调节的理解。这些知识将为改进治疗房颤体积异常的疗法奠定合理的基础，从而有助于降低胎儿和新生儿的发病率和死亡率。