Sustained gastroesophageal reflux (GER) causes airway inflammation and can be considered as a potential trigger of asthma. There are complex neural innervations and reflex mechanisms between trachea and esophagus, and close proximity between them also provide a chance that trachea and esophagus could heavily interact with each other. The studies of the interactions between trachea and esophagus began early, but how gastric contents in the esophagus cause airway inflammation are still not completely understood. In this study, we will observe the extent of airway inflammatory response of the Long Evans rats induced by intraesophageal infusion of different inflammatory agents. We simulated the condition of inflammatory substances in the esophagus by intraesophageal infusion of either capsaicin or 6-hydroxydopamine (6-OHDA). At the different time point after infusion of inflammatory substances, rats were sacrificed for the analysis of the amount of the plasma leakage in the lower airways and esophagus. The amount of plasma leakage was expressed by the area density of India ink-labeled leaky blood vessels in tissue whole mounts. From the previous studies, we realize that neural reflexes played an important role in GER-induced airway inflammation. In this research, we further studied whether vagus nerves were involved in this neural reflex pathway by the pretreatment of bilateral vagotomy. Free radicals generated by the oxidation of 6-OHDA and capsaicin damage the airway epithelium, and lead to the liberation of cellular contents and cytokines that will augment the inflammatory response. Free radicals also activate NF-£eB pathway and will further enhance the inflammatory response. We evaluate the extent of these free radicals involved in GER-induced airway inflammation, by pretreatment with a hydroxyl radical scavenger -dimethylthiourea (DMTU). Our results showed that plasma leakage in the airway increased time-dependently from 5 to 15 min after the infusion of 5 £gg/ml/kg of capsaicin. This response peaked at 15 min, and gradually diminished after 30 min of capsaicin application. Plasma leakage in the airways caused by the application of 10 mg/ml/kg of 6-OHDA also increased time-dependently and peaked at 30 min. We also demonstrated that the vagus nerve played an important role in GER-induced airway inflammation. Because bilateral vagotomy significantly alleviated the airway inflammatory response caused by the application of capsaicin. Free radicals also involved in this process, because pretreatment with (2.25 g/kg, i.v.) DMTU significantly lowered the amount of plasma leakage caused by capsaicin and 6-OHDA.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0621106-145615 |
| Date | 21 June 2006 |
| Creators | Chang, Wei-Pang |
| Contributors | Ying-Chun Chen, Chao-Cheng Liu, Hung-Tu Huang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0621106-145615 |
| Rights | withheld, Copyright information available at source archive |
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