LUNG EPITHELIAL ION TRANSPORT AFTER PREMATURE BIRTH

早产后肺上皮离子转运

• 批准号: 2835659
• 负责人: DAVID P CARLTON
• 金额: $ 29.42万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2835659
• 关键词: SDS polyacrylamide gel electrophoresis; biological fluid transport; chloride ion; ion transport; membrane activity; neutrophil; nitric oxide; northern blottings; polymerase chain reaction; premature infant animal; premature labor; pulmonary edema; pulmonary surfactants; respiratory distress syndrome of newborn; respiratory epithelium; sheep; sodium ion; sodium potassium exchanging ATPase; tissue /cell culture; western blottings

Pulmonary edema is a consistent pathological feature of the neonatal respiratory distress syndrome and it occurs when fluid enters the, lung at a rate greater than the rate at which fluid is cleared. Pulmonary edema reduces lung volume, impairs oxygenation, and increases the need for respiratory support. Previous studies have clarified that respiratory failure after premature birth is associated with excess fluid and protein entry into the lung with resultant alveolar flooding. It is unclear whether delayed clearance of fluid from the lung is an additional factor contributing to lung edema in the neonatal respiratory distress syndrome. Because transepithelial ion movement is responsible, at least in part, for clearance of fluid from the distal airspace, we hypothesize that abnormal lung epithelial ion transport contributes to alveolar edema by delaying fluid clearance from the distal airspaces. Our long-term goal is to improve our understanding of the mechanisms that contribute to respiratory failure after premature birth. In this proposal, our studies will include assessment of transmembrane Na and Cl flux and Na-K-ATPase activity in distal lung epithelial cells as well as the molecular bases for alterations in ion transport. We plan to (l) define the mechanism by which neutrophils impair ion transport in lung epithelial cells; (2) characterize the changes in lung epithelial ion transport that are induced by pulmonary surfactant; (3) evaluate the role of nitric oxide in regulating Cl secretory function in lung epithelium around the time of premature birth; (4) determine if Na and Cl transport and Na-K-ATPase activity are abnormal in lung epithelial cells in the respiratory distress syndrome of prematurity; and (5) determine if surfactant replacement at birth favorably influences Na and Cl transport and Na-K-ATPase activity in lung epithelial cells. We predict that factors important in the pathogenesis of neonatal respiratory distress syndrome impair Na transport, decrease Na-K-ATPase activity, and promote postnatal Cl secretory activity. Our expectation is that a more complete understanding of the factors that contribute to pulmonary edema and respiratory failure after premature birth will improve our ability to design strategies and interventions that will reduce the severity of neonatal respiratory distress and diminish the adverse outcomes associated with this condition.

肺水肿是新生儿呼吸窘迫综合征的一贯病理特征，当液体以大于液体清除速率的速率进入肺时发生肺水肿。肺水肿减少肺容量，损害氧合，并增加对呼吸支持的需求。先前的研究已经阐明，早产后呼吸衰竭与过量的液体和蛋白质进入肺内导致肺泡泛洪有关。目前尚不清楚肺液体清除延迟是否是新生儿呼吸窘迫综合征肺水肿的另一个因素。因为跨上皮离子运动至少部分地负责从远端气腔清除液体，我们假设异常的肺上皮离子转运通过延迟从远端气腔清除液体而导致肺泡水肿。我们的长期目标是提高我们对早产后呼吸衰竭机制的理解。 在这个建议中，我们的研究将包括跨膜Na和Cl通量和Na-K-ATP酶活性的远端肺上皮细胞的评估，以及在离子转运的改变的分子基础。本研究拟（1）阐明中性粒细胞损害肺上皮细胞离子转运的机制，（2）研究肺表面活性物质对肺上皮细胞离子转运的影响，（3）探讨一氧化氮在早产前后对肺上皮细胞氯离子分泌功能的调节作用，（4）探讨一氧化氮对肺上皮细胞氯离子分泌功能的影响。（4）早产儿呼吸窘迫综合征肺上皮细胞Na、Cl转运及Na-K-ATP酶活性是否异常;和（5）确定出生时表面活性剂替代是否有利地影响肺上皮细胞中Na和Cl转运和Na-K-ATP酶活性。我们预测，在新生儿呼吸窘迫综合征的发病机制的重要因素损害钠转运，降低钠-钾-ATP酶的活性，并促进出生后的Cl分泌活性。我们的期望是，更全面地了解导致早产后肺水肿和呼吸衰竭的因素将提高我们设计策略和干预措施的能力，这些策略和干预措施将降低新生儿呼吸窘迫的严重程度，并减少与这种情况相关的不良后果。