DE PEDIATRIC COBRE: OXYGEN AND BAROTRAUMA EFFECTS ON HUMAN AIRWAY EPITHELIUM

DE PEDIATRIC COBRE：氧气和气压伤对人体气道上皮的影响

• 批准号: 8168445
• 负责人: Aaron Chidekel
• 金额: $ 23.93万
• 依托单位: ALFRED I. DU PONT HOSP FOR CHILDREN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168445
• 关键词: Acute; Affect; Anti-Bacterial Agents; Apoptotic; Borderline Personality Disorder; Bronchopulmonary Dysplasia; Childhood; Chronic lung disease; Clinical; Clinical Treatment; Computer Retrieval of Information on Scientific Projects Database; Critical Illness; Development; Disease; Dysbarism; Funding; Grant; Human; Hyperoxia; Inflammation; Inflammation Mediators; Institution; Life; Lung; NF-kappa B; Necrosis; Neonatal; Neonatal Intensive Care; Outcome; Oxygen; Pathogenesis; Pathway interactions; Perinatal; Pharmaceutical Preparations; Premature Birth; Process; Research; Research Personnel; Resources; Role; Sepsis; Source; United States National Institutes of Health; airway epithelium; airway remodeling; cell injury; congenital heart disorder; infancy; oxygen toxicity; pre-clinical; stem

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. Despite remarkable advances in perinatal and neonatal intensive care, chronic lung disease remains a common occurrence after premature birth or critical illness in the neonatal period or early infancy. Chronic lung disease of infancy (CLDI), as it is now frequently referred to, encompasses a heterogeneous group of conditions stemming from severe illness in the neonatal period or early in life, which often includes disorders other than those primarily affecting the lung. The treatment of an acute non-pulmonary illness, such as sepsis or congenital heart disease, may result in CLDI2. The overall thrust of this proposal is to study key components of the pathogenesis of BPD and CLDI. To do this, we will focus on two specific factors that contribute importantly to the development of chronic lung disease, oxygen toxicity (hyperoxia) and barotrauma. We will focus on outcomes that are highly relevant to the development of BPD and CLDI. These will include assessment of mediators of inflammation, innate antibacterial factors in the airway, the airway remodeling process and histological evidence of both necrotic and apoptotic cell injury. Intracellular regulatory mechanisms will also be evaluated focusing on the central role of the NF-kb pathway in inflammation. Finally, through the selective use of important clinical and pre-clinical treatments, we will assess the potential usefulness of these drugs and strategies and explore their mechanisms of action at the cellular level.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管在围产期和新生儿重症监护方面取得了显著进展，但在早产或新生儿期或早期危重疾病之后，慢性肺部疾病仍然是常见的。婴儿期慢性肺病(CLDI)，如现在经常提到的，包括一组由新生儿期或生命早期严重疾病引起的各种疾病，通常包括主要影响肺部的疾病以外的其他疾病。治疗急性非肺病，如败血症或先天性心脏病，可能会导致CLDI2。 这项建议的总体主旨是研究BPD和CLDI发病机制的关键组成部分。为此，我们将重点关注导致慢性肺部疾病发展的两个特定因素，即氧气中毒(高氧)和气压创伤。我们将重点关注与BPD和CLDI发展高度相关的成果。这些将包括评估炎症介质、呼吸道中的先天抗菌因子、气道重塑过程以及坏死和凋亡细胞损伤的组织学证据。细胞内的调节机制也将被评估，重点是核因子-kb通路在炎症中的核心作用。最后，通过有选择地使用重要的临床和临床前治疗方法，我们将评估这些药物和策略的潜在有用性，并探索它们在细胞水平上的作用机制。