RESUMEN
BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) has been linked to a number of extra-esophageal symptoms and disorders, primarily in the respiratory tract. Current animal models of reflux esophagitis are adapted to diseases of the digestive system, rather than to reflux-associated respiratory symptoms. The aim of this study was to evaluate a novel external esophageal perfusion model to induce esophageal, tracheal and pneumonic histological injury similar to that associated with GERD. METHODS: Twenty guinea pigs were randomized to the acid-treated or PBS-treated group. Esophageal catheters were used to perfuse the esophageal lumen of guinea pigs with hydrochloric acid containing 1 g/l pepsin or PBS for 14 days. The total cell number and cell differential counts in bronchoalveolar lavage fluid (BALF) were determined 24 h after the last perfusion. Histological changes in the esophageal, tracheal and pneumonic tissues were observed by hematoxylin-eosin staining. RESULTS: The numbers of lymphocytes, eosinophils and total inflammatory cells in the BALF were significantly higher in acid-perfused than PBS-perfused animals. Histological evidence suggested esophageal and pneumonic inflammations were prominent in acid-treated animals. CONCLUSION: Repetitive, acid-perfused, esophageal events copied the animal models of reflux esophagitis, and elicited inflammatory responses in the airways and lungs of guinea pigs.
Asunto(s)
Esofagitis Péptica/complicaciones , Esófago , Reflujo Gastroesofágico/complicaciones , Pulmón , Perfusión , Enfermedades Respiratorias/etiología , Tráquea , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Esofagitis Péptica/inducido químicamente , Esofagitis Péptica/inmunología , Esofagitis Péptica/patología , Esófago/inmunología , Esófago/patología , Estudios de Factibilidad , Femenino , Reflujo Gastroesofágico/inducido químicamente , Reflujo Gastroesofágico/inmunología , Reflujo Gastroesofágico/patología , Cobayas , Ácido Clorhídrico , Pulmón/inmunología , Pulmón/patología , Masculino , Pepsina A , Enfermedades Respiratorias/inmunología , Enfermedades Respiratorias/patología , Factores de Tiempo , Tráquea/inmunología , Tráquea/patologíaRESUMEN
OBJECTIVE: To observe the expression of substance P (SP) in the airway mucosa of guinea pigs with repetitive esophageal stimulation by hydrochloric acid (HCL). METHODS: Twenty adult guinea pigs were randomly divided into 2 groups (n = 10 each): (1) The HCL model group: On the day of experimentation, guinea pigs were maintained under ketamine anesthesia. A 5F catheter was inserted orally into the lumen of the middle and lower esophagus. The esophagus of each animal was perfused with HCl-P for 20 min/d for 14 d. (2) The PBS control group: The esophagus of each animal was perfused with PBS instead. The bronchial responsiveness to Ach given intravenously with increasing doses (3.125, 6.25, 12.5, 25, 50, 100 microg/kg) was measured after the last perfusion. The left lung was isolated for pathological examination. Lung sections were stained with hematoxylin and eosin, and other sections were prepared for immunohistochemistry using monoclonal antibodies against SP. RESULTS: In response to increasing doses of ACh, all guinea pigs showed dose-dependent increases in R(L). However, when the dose of ACh was increased to 25 microg/kg, the airway responsiveness increased significantly in the HCl-P model animals compared with the PBS control group (t values = 43.057, 51.410, 57.359 respectively, all P<0.01). The mean gray values of SP decreased significantly in the tracheal epithelia and the distal airway walls of the model group compared with the PBS control group (t values = 3.44, 2.16 respectively, all P<0.01). CONCLUSION: There was airway neurogenic inflammation in guinea pigs with repetitive esophageal stimulation by HCL, which maybe closely related to the pathogenesis of gastro-esophageal reflux disease.