LUNG DEFENSE MECHANISMS FROM ENVIRONMENTAL OZONE

环境臭氧的肺部防御机制

• 批准号: 6178717
• 负责人: EDWARD S SCHELEGLE
• 金额: $ 21.9万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-04 至 2002-03-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6178717
• 关键词: C fiber; action potentials; afferent nerve; environmental toxicology; immunocytochemistry; inflammation; laboratory rat; lung alveolus; lung injury; mucosal immunity; neuropeptides; neurophysiology; oxidative stress; ozone; pulmonary respiration; pulmonary stretch receptors; respiratory airflow measurement; respiratory epithelium; respiratory toxin; statistics /biometry; substance K; substance P; tachykinin; transmission electron microscopy

DESCRIPTION (Adapted from the Investigator's Abstract): The proposed research is aimed at testing four specific hypotheses related to the mechanism(s) through which ozone induced lung afferent C fiber excitation serves to protect the small distal airways and alveoli from oxidant injury and inflammation. The specific hypotheses are as follows. 1) In rats, acute inhalation of ozone excites lung C fibers to evoke a rapid shallow breathing pattern, which in turn acts to limit deep lung penetration of ozone and, therefore, reduces ozone induced peripheral airway injury. This hypothesis will be tested by examining the effects of ozone induced reflex changes in breathing pattern and lung mechanics have on the distribution and severity of ozone induced airway after selective blockage of C fibers traversing the vagus nerve. 2) In rats, acute inhalation of ozone will exclusively excite lung C fibers. This will be tested by recording action potentials from all known lung afferents during ozone inhalation. 3). Airway deposition of ozone and subsequent epithelial injury in rats is influenced by breathing pattern. This hypothesis will be tested in paralyzed, normal rats in which breathing frequency is controlled at 80 and 120 breaths/min by negative pressure ventilation and evaluation of nasal, tracheal, proximal bronchial, distal bronchial and terminal bronchiolar airways for 18 oxygen labeled ozone incorporation and airway pathology. 4). Lung C fibers enhance inflammation induced by acute ozone exposure by releasing neuropeptides in airway walls that act to increase airway vascular permeability and the influx of neutrophils. This shall be tested by (a) comparing the effects of ozone inhalation on lung inflammation in normal rats and rats that totally lack sensory C fibers, and (b) comparing lung inflammation following ozone inhalation among several groups of rats, each pretreated with a different neurokinin receptor antagonist. It is anticipated that the information derived from these studies will better define the effects that lung C fibers stimulation evokes during acute ozone exposure.

描述（改编自研究者摘要）：拟定的 这项研究旨在测试四个具体的假设， 臭氧诱导肺传入C纤维兴奋的机制 用于保护小的远端气道和肺泡免受氧化剂损伤 和炎症。 具体假设如下。 1)在大鼠中， 急性吸入臭氧可刺激肺C纤维，引起快速浅 呼吸模式，这反过来又限制了肺部的深层渗透， 臭氧并因此减少臭氧引起的外周气道损伤。 这 将通过检查臭氧引起的反射的影响来检验假设 呼吸模式和肺力学的变化对分布和 选择性阻断C纤维后臭氧诱导的气道严重程度 穿过迷走神经 2)在大鼠中，急性吸入臭氧将 只兴奋肺C纤维。 这将通过记录动作进行测试 臭氧吸入过程中所有已知的肺传入电位。 （3）第三章。 臭氧在大鼠气道沉积及随后的上皮损伤 受呼吸模式的影响。 这一假设将在 麻痹的正常大鼠，其中呼吸频率控制在80， 120次/分负压通气和鼻评价， 气管、近端支气管、远端支气管和末端细支气管 气道18氧标记的臭氧掺入和气道病理学。 4）。 肺C纤维增强急性臭氧暴露引起的炎症反应 在气道壁释放神经肽， 渗透性和中性粒细胞的流入。 应通过（a）进行测试 臭氧吸入对正常人肺部炎症的影响 大鼠和完全缺乏感觉C纤维的大鼠，和（B）比较肺 在几组大鼠中， 用不同的神经激肽受体拮抗剂预处理。 是 预计从这些研究中获得的信息将更好地 定义急性臭氧期间肺C纤维刺激引起的影响 exposure.