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: 7932359
• 负责人: Sadis Matalon
• 金额: $ 2.5万
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932359
• 关键词: Agonist; Albumins; Alveolar; Animals; Antioxidants; Arts; Biochemical; Centers of Research Excellence; Chlorine; Data; Epithelial; Epithelium; Exposure to; Grant; Injury; Liquid substance; Lung; Measurement; Mus; Nitrites; Ovum; Physiological; Play; Rattus; Recovery; Reduced Glutathione; Research Personnel; Respiratory System; Respiratory syncytial virus; Role; Seminal; Series; Signal Transduction; Sodium Channel; Talents; Toxic effect; ascorbate; epithelial Na+ channel; novel; pulmonary function; receptor; research study; respiratory

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, /32 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）： 这个卓越研究中心（RCE）题为：“氯诱发对心脏呼吸系统的损伤的新型治疗方法”由三个项目和两个核心组成。 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肺和全身血管的精彩功能妥协。此外，我们建议在感染呼吸道综合病毒或用卵子白蛋白挑战的动物中，C12的这些毒性作用将增强。在我们的第一个实验中，我们将在RSV受感染的RSV和OVA中挑战小鼠以及C12暴露于C12暴露之前和之后的正常大鼠中，在RSV感染中挑战了许多最先进的生物化学，生物物理，生理和形态测量值，以记录对肺部表皮和肺部和肺部和系统性干扰素的发作和进展。然后，我们将用抗氧化剂，TRP拮抗剂， /32激动剂和亚硝酸盐治疗C12后C12接触后的各个间隔，或通过气溶解或通过雾化或腹膜内（抗氧化剂和亚硝酸盐）和特定功能测量来量化恢复。 RCE的强调包括研究人员的不同才能，独特的设施以及初步数据的新颖性。这三个项目（其中两个基于现有UO1赠款产生的新发现）得到了行政核心和曝光核心的支持，这些核心通过提供基本功能（例如将动物接触到C12）并帮助将团队整合到凝聚力的实体中，从而发挥关键作用。