持續性的胃液逆流到食道可能會造成呼吸道的發炎反應，也被認定為是引起氣喘的潛在因子之一。氣管與食道之間有著複雜的神經分布以及神經反射機制，且氣管與食道鄰近的位向也使它們能夠有足夠多的互動，但是存在於食道當中的酸性胃液是如何造成呼吸道發炎的反應機制仍然未被透徹的研究。在本次研究當中，我們在大鼠的食道當中灌滴不同的發炎物質，並且觀察大鼠呼吸道發炎反應的產生以及程度上的變化，我們在食道內灌滴辣椒素或6-羥多巴胺以模擬胃液或其他發炎物質在食道當中的情況，在經過不同的時間點之後，犧牲大鼠並且觀察並量化其下呼吸道以及食道的血漿滲漏狀況。血漿滲漏量化的計量方法是在整裝標本計算以印地安追蹤染劑標定的血漿滲漏血管的區域面積密度。過去的研究當中指出神經反射在由胃液逆流所引發的呼吸道發炎反應當中扮演了重要的角色，在本次研究當中我們藉由雙側迷走神經切除術進一步的探討迷走神經是否參與在此神經反射當中。辣椒素或6-羥多巴胺氧化所產生的自由基會破壞細胞膜，並且使細胞激素釋出而加重發炎反應；自由基也會活化NF-κB訊息傳遞路徑而進一步的使發炎反應變嚴重。我們以自由基清除劑二甲基硫尿素做前處理，以判斷自由基是否有參與在由胃液逆流到食道所引發的呼吸道發炎反應。我們的結果顯示出在食道灌滴5 μg/ml/kg的辣椒素會造成大鼠下呼吸道的發炎反應，此發炎反應在給辣椒素刺激之後的五到十五分鐘呈現線性增加，並且在十五分鐘後達到最高點，在三十分鐘後就開始逐漸下降。由10/mg/ml/kg 6-羥多巴胺所誘發的呼吸道發炎反應也隨時間增加，但發炎反應最嚴重的情況發生在給6-羥多巴胺刺激之後的三十分鐘。我們也證明了迷走神經確實參與了氣管與食道之間的神經反射機制，因為雙側迷走神經切除前處理可以有效的抑制在大鼠下呼吸道由辣椒素誘導所產生的發炎反應。自由基也參與了在此發炎反應當中，因為二甲基硫尿素的前處理可以有效抑制由辣椒素或6-羥多巴胺所誘發的下呼吸道血漿滲漏反應。

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-κB 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 μg/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.

Abstract
摘要
Introduction
Purpose of study
Materials and Methods
Results
Discussion
Conclusion
References
Figures & Tables

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