Lung Preservation for Transplantation

移植时的肺保存

• 批准号: 6920767
• 负责人: George Alexander Patterson
• 金额: $ 38.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6920767
• 关键词: Adenoviridae; apoptosis; clinical research; enzyme linked immunosorbent assay; free radical oxygen; gene delivery system; gene expression; gene therapy; human subject; inflammation; interleukin 10; laboratory rat; lung; lung injury; lung ischemia /hypoxia; lung transplantation; nuclear factor kappa beta; polymerase chain reaction; reperfusion; terminal nick end labeling; tissue /organ preservation; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): Ischemia-reperfusion (I/R) injury continues to cause significant morbidity and mortality in lung transplantation. Two important pathways which significantly contribute to ischemia-reperfusion injury are the inflammatory response and apoptosis. The transcription factor nuclear factor-kappa B (NF-KappaB) is critical for the maximal expression of many pro-inflammatory mediators. NF-KappaB is also a critical regulator of apoptosis, or programmed cell death. The activation of NF-KappaB is important in the pathogenesis of acute lung injury typical of I/R injury. The overexpression of the anti-inflammatory cytokine Interleukin-10 (IL-10) in experimental lung grafts is effective in significantly ameliorating I/R injury. The aim of this proposal is to study the role of NF-KappaB activation in I/R injury following experimental lung transplantation and the mechanisms by which the overexpression of IL-10 alters these events. An orthotopic rodent left lung transplantation model has proved to be a productive and reliable in vivo model for this investigation. Adenoviral gene transfer of IL-10 by the endobronchial route is an efficient means of establishing IL-10 overexpression in experimental lung grafts. The first aim of this project is to examine the role of NF-KappaB activation in I/R injury. The second aim of this project is to investigate the mechanisms by which gene transfer of IL-10 ameliorates I/R injury.

描述（由申请人提供）： 缺血再灌注（I/R）损伤持续导致肺移植中显著的发病率和死亡率。炎症反应和细胞凋亡是导致缺血再灌注损伤的两条重要途径。转录因子核因子-κ B（NF-κ B）对于许多促炎介质的最大表达至关重要。NF-KappaB也是细胞凋亡或程序性细胞死亡的关键调节因子。NF-κ B的活化在I/R损伤的典型急性肺损伤的发病机制中是重要的。实验性肺移植物中抗炎细胞因子白细胞介素-10（IL-10）的过表达可有效地显著改善I/R损伤。本研究的目的是研究NF-κ B活化在实验性肺移植后I/R损伤中的作用，以及IL-10过表达改变这些事件的机制。原位啮齿动物左肺移植模型已被证明是一个生产力和可靠的体内模型，这项调查。腺病毒介导的IL-10基因转移是一种建立实验性肺移植物中IL-10过表达的有效方法。本项目的第一个目的是研究NF-κ B激活在I/R损伤中的作用。本课题的第二个目的是研究IL-10基因转移改善I/R损伤的机制。