Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands;
Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands;
Am J Physiol Gastrointest Liver Physiol. 2014 Aug 1;307(3):G323-9. doi: 10.1152/ajpgi.00345.2013. Epub 2014 Jun 12.
Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin.
在胃食管反流病患者中，已经描述了食管敏感性增加和黏膜完整性受损，但两者之间的关系尚不清楚。本研究旨在调查侵蚀性和非侵蚀性反流病患者的酸敏感性，以确定其与功能性食管黏膜完整性变化的关系，并研究这些患者黏膜完整性受损的细胞机制。在这项前瞻性实验研究中，12 例非侵蚀性反流病患者、12 例食管炎 A 或 B 级患者和 11 例健康对照者接受了酸灌注试验和上内窥镜检查。在胃镜检查过程中，通过电组织阻抗谱测量黏膜完整性，并在 Ussing 室中分析活检标本的跨上皮电阻、跨上皮通透性以及紧密连接蛋白和丝聚合蛋白基因的表达。与对照组相比，非侵蚀性反流病和食管炎患者对酸灌注更敏感，其烧心感知时间更短，烧心感知强度更高。在反流病患者中，增强的酸敏感性与体内和体外食管黏膜完整性受损有关。食管炎患者的黏膜完整性明显受损，表现为跨上皮通透性增加和细胞外阻抗降低。尽管在反流病患者的活检中未发现紧密连接蛋白表达有显著差异，但黏膜完整性参数与丝聚合蛋白的表达呈负相关。总之，胃食管反流病患者的酸敏感性增强，与存在侵蚀性无关，且与食管黏膜完整性受损有关。食管黏膜完整性与丝聚合蛋白的表达有关。
