盐酸灌注豚鼠食管诱导气道血管微渗漏和神经源性炎症

Airway neurogenic inflammation and microvascular leakage induced by HCl intra-oesophageal instillation in guineapigs

目的胃食管反流(GER)是常见的临床病症,并与多种呼吸系统疾病有关,包括慢性咳嗽和支气管哮喘等,其发病机制尚未明确。通过观察盐酸灌注食管是否可以引起气道速激肽释放和气道血浆渗出,旨在探讨GER性咳嗽的发病机制。方法动物预先给予阿托品和心得安处理,给麻醉豚鼠食管灌注1mol/L盐酸,分别观察气管、主支气管、细支气管的气道微血管血浆渗出的变化,气道血浆渗出测定采用伊文思蓝法;并观察应用神经内肽酶抑制剂磷阿米酮、神经肽1受体拮抗剂FK888、SR140333对盐酸灌注豚鼠食管气管、主支气管、细支气管的气道微血管血浆渗出的影响。结果灌注盐酸入食管可以显著增加气道血浆渗出。磷阿米酮可以显著增加盐酸灌注食管引起的气管、主支气管、细支气管血浆渗出,FK888、SR140333可以显著抑制气道血浆渗出。在双侧迷走神经切断组,神经内肽酶增强的气道血浆渗出能被明显抑制。结论①食管灌注盐酸通过诱导气道速激肽释放引起气道神经源性炎症;②食管和气管之间有神经通路相联系,RARs和C神经纤维参与盐酸灌注食管所致的气道血浆渗出;③该食管-支气管反射可能是GER诱发咳嗽的重要机制。

Objective Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, such as chronic cough, asthma, hut its mechanisms is still not clear. The study is to observe the microvaseular leakage of trachea,main bronchi and bronchial in quineapigs by HCl intra-oesophageal instillation, and investigate the mechanisms of GER induced cough. Methods The microvascular leakage was examined induced by intraesophageal 1N HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-reeeptor antagonist FK888 or SR140333 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Data are reported as mean± SD. Results Infusion of 1N HCl into the esophagus significantly increased plasma extravasation in the trachea and main bronchi （from 11.43±4.79,8.80±2.05 to 30.90± 13.14,24.32± 17.43,respeetively, P 〈0.001）. Phosphoramidon significantly potentiated plasma extravasation in the trachea,main bronchi and bronchial （ 84. 83 ± 29. 07, 82.76±32.54,45.95±8.13, P 〈0. 001 ） , whereas the extravasation were significantly inhibited in FK888 （23.11±8.94,19.2±14.31,18.83 ± 9.31） and SR140333 group （32.96± 12.34,21.01± 19. 13,20.03±12.53）（P〈0.001）. Tracheal plasma extravasation potentiated by phosphoramidon was also significantly inhibitedin the bilateral vagotomized animals （ 35.3 ±9.6 , 23.09 ± 13.39 , 24.01 ±12.39 , P 〈 0. 001 ） .Conclusions These results suggest that ①Tachykinin are released to cause plasma extravasation in the airways as a result of intra esophageal HCI stimulation.②There are neural pathways communicating between the esophagus and airways, including the RARs and C fibers. ③The esophagus-airways reflex is very likely the important mechanisms of GER cough.