Adaptation of esophageal mucosa to acid- and pepsin-induced damage - Role of nitric oxide and epidermal growth factor

被引:47
作者
Lanas, AI [1 ]
Blas, JM [1 ]
Ortego, J [1 ]
Soria, J [1 ]
Sainz, R [1 ]
机构
[1] UNIV ZARAGOZA,GASTROENTEROL SERV,HOSP CLIN,UNIDAD MIXTE INVEST,E-50009 ZARAGOZA,SPAIN
关键词
esophagitis; acid; pepsin; adaptation; epidermal growth factor; nitric oxide;
D O I
10.1023/A:1018837003196
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
To study whether the esophageal mucosa was able to elicit mucosal adaptation, we induced esophageal damage by perfusing acidified pepsin in rabbits. Mucosal adaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline) for 60 min prior to acidified pepsin (strong irritant). Macroscopic and microscopic esophageal injury, cell proliferation, and mucosal barrier function (H+, K+, hemoglobin flux rates) were studied. Preexposure of the esophageal mucosa to acidified saline significantly decreased both the mucosal damage and the mucosal barrier dysfunction induced by acidified pepsin. The development of this phenomenon was nondependent on cell proliferation. Concomitant treatment with either the nitric oxide synthase inhibitor, N-G-nitro-L-arginine, or the perfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, an inhibitor of the tyrosine kinase activities ligated to the intracytoplasmatic domain of the EGF receptor, during the preexposure period completely reversed the protection induced by acid. We conclude that the rabbit esophageal mucosa shows mucosal adaptation to acid and pepsin. The development of this phenomenon is fast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxide and EGF-receptor-mediated mechanisms.
引用
收藏
页码:1003 / 1012
页数:10
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