REGULATION OF THE DUCTUS ARTERIOSUS

动脉导管的调节

• 批准号: 7716048
• 负责人: RONALD I CLYMAN
• 金额: $ 2.26万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716048
• 关键词: Anatomy; Birth; Bronchopulmonary Dysplasia; Cell Death; Cessation of life; Closure; Computer Retrieval of Information on Scientific Projects Database; Development; Ductus Arteriosus; Event; Funding; Grant; Growth Factor; Human; Hypoxia; Incidence; Indomethacin; Infant; Institution; Left; Mechanical ventilation; Messenger RNA; Migration Assay; Modeling; Morbidity - disease rate; Necrotizing Enterocolitis; Newborn Infant; Nitric Oxide; Papio; Patent Ductus Arteriosus; Patients; Population; Pregnancy; Premature Infant; Process; Prostaglandin Antagonists; Prostaglandins; Regulation; Research; Research Personnel; Resources; Severities; Smooth Muscle Myocytes; Source; Techniques; Testing; United States National Institutes of Health; Week; day; in vivo; migration; postnatal; protein expression; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the premature infant, the ductus arteriosus frequently remains open for many days or weeks after delivery. As many as 70% of newborns delivered prior to 28 weeks gestation will require some form of therapy to close their patient ductus. If left unclosed, a persistent patent ductus arteriosus is associated with significant morbidity: bronchopulmonary dysplasia (with its prolonged need for mechanical ventilation) and necrotizing enterocolitis. Numerous studies have shown that early closure of the ductus arteriosus decreases the severity of bronchopulmonary dysplasia and decreases the incidence of necrotizing enterocolitis. Although inhibitors of prostaglandin synthesis, like indomethacin, induce ductus closure in 85% of preterm infants in whom they are used, ductus reopening occurs in 20-30% of treated infants. Recent studies demonstrate that the postnatal development of ductus wall hypoxia is an essential step in the anatomic remodeling (luminal endothelial proliferation, migration, and smooth muscle cell death) that leads to permanent closure. The studies proposed in this application will examine the mechanisms involved in early, spontaneous ductus closure in the full-term newborn and those involved in the delayed closure of the premature baboon model of persistent patent ductus arteriosus, which is the only model that mimics the long-term events surrounding ductus patency in the preterm human. They will examine the hypothesis that vasoactive factors that alter ductus tone (e.g., prostaglandins, nitric oxide) also interact with an deregulate the growth factors and death factors involved in anatomic remodeling. They will examine mechanisms to increase ductus wall hypoxia in the preterm newborn. They will use immunohistochemical, Western, and Northern techniques to study changes in mRNA and protein expression; they will use assays of cell migration, proliferation, and cell death in isolated vessels, endothelial and smooth muscle cells in culture. They will characterize changes in receptor populations and test their findings in vivo. These studies should increase our understanding of what initiates and sustains the process of ductus closure after birth and why it does not occur in the preterm infant.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在早产的婴儿中，动脉导管经常在分娩后几天或几周内保持开放。 在妊娠28周之前，多达70％的新生儿需要某种形式的治疗才能关闭其患者管道。 如果未锁定，则持续的专利导管动脉静脉曲张与明显的发病率有关：支气管肺发育异常（对机械通气的需求延长）和坏死性肠结肠炎。 大量研究表明，动脉导管的早期关闭可降低支气管肺发育不良的严重程度，并降低坏死性小肠结肠炎的发生率。 尽管前列腺素合成的抑制剂（如吲哚美辛）诱导了85％使用的早产儿的导管闭合，但在20-30％的治疗婴儿中，导管重新开放。最近的研究表明，导管壁缺氧的产后发展是解剖重塑（腔内内皮内皮增殖，迁移和平滑肌细胞死亡）的重要步骤，导致永久闭合。 本应用程序中提出的研究将检查完美新生儿中早期自发性导管封闭的机制，以及参与延迟闭合的持续过早狒狒模型的持续专利Ductent Ductus Arteriosus模型的机制，这是唯一模拟早产围绕着围绕着体验的长期事件的模型。 他们将研究以下假设：改变导管张力的血管活性因子（例如前列腺素，一氧化氮）也与解剖学的解剖因子和死亡因子相互作用。 他们将检查增加早产新生儿导管壁缺氧的机制。 他们将使用免疫组织化学，西方和北方技术来研究mRNA和蛋白质表达的变化。他们将在培养物中使用细胞迁移，增殖和细胞死亡的测定法，内皮和平滑肌细胞。 他们将表征受体群体的变化并在体内测试其发现。 这些研究应加深我们对出生后导管闭合过程的启动和维持的理解，以及为什么它在早产儿中不发生。