Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems-U54

氯引起的心肺系统损伤的新疗法-U54

• 批准号: 7857985
• 负责人: Sadis Matalon
• 金额: $ 112.46万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7857985
• 关键词: Novel; Treatments; Chlorine; Induced; Injury

DESCRIPTION (provided by applicant): This Research Center of Excellence (RCE) entitled: "Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems" consists of three projects and two cores. The unifying theme spanning all projects is that exposure of animals to C12 results in the formation of reactive intermediates which deplete ascorbate and reduced glutathione in the lung epithelial fluids, damage key components of the respiratory and alveolar epithelial [such as transient receptor protein (TRP) and epithelial sodium channels (ENaC)] and then, via inhibition of eNOS signaling compromise seminal functions of the pulmonary and systemic vasculatures. Furthermore, we propose that these toxic effects of C12 will be heightened in animals infected with respiratory syncytial virus or challenged with ova albumin. In our first series of experiments we will perform a number of state of the art biochemical, biophysical, physiological and morphometric measurements in RSV infected and ova albumin challenged mice as well as normal rats prior to and following C12 exposure to document the onset and progression of injury to lung epithelia and pulmonary and systemic vasculature. We will then treat them with antioxidants, TRP antagonists, B2 agonists and nitrite administered at various intervals post C12 exposure either intra-tracheally or via aerosolization or intraperitoneally (antioxidants and nitrite) and quantify recovery by specific functional measurements. Strong points of the RCE include the diverse talents of the investigators, the unique facilities, and the novelty of the preliminary data. The three projects (two of which build on novel findings generated by existing UO1 grants) are supported by an administrative core and the exposure core, which play key roles by both providing essential functions (such as exposure of animals to C12) and helping to integrate the team into a cohesive entity.

描述（由申请人提供）： 该卓越研究中心 (RCE) 的题为：“氯引起的心肺系统损伤的新型治疗方法”，由三个项目和两个核心组成。所有项目的统一主题是，动物接触 C12 会导致反应性中间体的形成，这些中间体会消耗肺上皮液中的抗坏血酸和还原型谷胱甘肽，损害呼吸道和肺泡上皮的关键成分[例如瞬时受体蛋白 (TRP)和上皮钠通道 (ENaC)]，然后通过抑制 eNOS 信号传导损害肺和全身脉管系统的精液功能。此外，我们认为，在感染呼吸道合胞病毒或受到卵白蛋白攻击的动物中，C12 的这些毒性作用将会加剧。在我们的第一个系列实验中，我们将在接触 C12 之前和之后对 RSV 感染和卵白蛋白攻击的小鼠以及正常大鼠进行许多最先进的生化、生物物理、生理和形态测量，以记录 C12 暴露之前和之后的情况。肺上皮以及肺和全身脉管系统损伤。然后，我们将在 C12 暴露后的不同时间间隔通过气管内或通过雾化或腹膜内（抗氧化剂和亚硝酸盐）给予抗氧化剂、TRP 拮抗剂、B2 激动剂和亚硝酸盐来治疗它们，并通过特定功能测量来量化恢复情况。 RCE的优点包括调查人员的多样化才能、独特的设施以及初步数据的新颖性。这三个项目（其中两个以现有 UO1 赠款产生的新发现为基础）得到了行政核心和接触核心的支持，它们通过提供基本功能（例如使动物接触 C12）和帮助整合发挥着关键作用。使团队成为一个有凝聚力的整体。