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: 7382177
• 负责人: Aaron Chidekel
• 金额: $ 5.49万
• 依托单位: ALFRED I. DU PONT HOSP FOR CHILDREN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382177
• 关键词: DE; PEDIATRIC; COBRE; OXYGEN; BAROTRAUMA

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管围产期和新生儿重症监护取得了显著进展，但慢性肺病仍然是早产后或新生儿期或婴儿期重症后的常见疾病。现在经常提到的婴儿期慢性肺病（CLDI）包括由新生儿期或生命早期严重疾病引起的一组异质性疾病，其中通常包括主要影响肺部的疾病以外的疾病。急性非肺部疾病的治疗，如败血症或先天性心脏病，可能导致CLDI2。本提案的总体主旨是研究BPD和CLDI发病机制的关键组成部分。为此，我们将重点关注对慢性肺部疾病发展有重要贡献的两个特定因素，氧毒性（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。这些将包括炎症介质的评估，气道内的先天抗菌因子，气道重塑过程以及坏死和凋亡细胞损伤的组织学证据。细胞内调节机制也将被评估，重点关注NF-kb通路在炎症中的核心作用。最后，通过选择性使用重要的临床和临床前治疗，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。