Souza Rhonda F, Huo Xiaofang, Mittal Vivek, Schuler Christopher M, Carmack Susanne W, Zhang Hui Ying, Zhang Xi, Yu Chunhua, Hormi-Carver Kathy, Genta Robert M, Spechler Stuart J
Department of Medicine, VA North Texas Health Care System and University of Texas Southwestern Medical School, Irving, Texas, USA.
Gastroenterology. 2009 Nov;137(5):1776-84. doi: 10.1053/j.gastro.2009.07.055. Epub 2009 Aug 4.
BACKGROUND & AIMS: Reflux esophagitis is believed to be caused by the caustic effects of refluxed gastric acid on esophageal epithelial cells. However, caustic chemical injuries develop rapidly whereas esophagitis might not appear until weeks after the induction of reflux in animal models. We studied early histologic events in the development of reflux esophagitis in a rat model and performed in vitro experiments to determine whether exposure to acidified bile salts causes esophageal epithelial cells to secrete chemokines that might contribute to inflammation.
At various time points after esophagoduodenostomy, the rat esophagus was removed and inflammatory changes were analyzed by histologic analyses. Human esophageal squamous cell lines were exposed to acidified bile salts to evaluate their effects on cytokine production and immune-cell migration.
Reflux esophagitis started at postoperative day 3 with lymphocytic infiltration of the submucosa that progressed to the epithelial surface-these findings contradicted those expected from a caustic chemical injury. Basal cell and papillary hyperplasia preceded the development of surface erosions. Exposure of squamous cells to acidified bile salts significantly increased the secretion of interleukin-8 and interleukin-1beta; conditioned media from these cells caused significant increases in the migration rates of T cells and neutrophils.
These findings support, but do not prove, an alternative concept for the development of reflux esophagitis in which refluxed gastric juice does not directly damage the esophagus, but rather stimulates esophageal epithelial cells to secrete chemokines that mediate damage of esophageal tissue.
反流性食管炎被认为是由反流的胃酸对食管上皮细胞的腐蚀作用所致。然而，腐蚀性化学损伤发展迅速，而在动物模型中，食管炎可能直到反流诱导数周后才会出现。我们研究了大鼠模型中反流性食管炎发展过程中的早期组织学事件，并进行了体外实验，以确定暴露于酸化胆汁盐是否会导致食管上皮细胞分泌可能促成炎症的趋化因子。
在食管十二指肠吻合术后的不同时间点，取出大鼠食管，通过组织学分析来分析炎症变化。将人食管鳞状细胞系暴露于酸化胆汁盐中，以评估其对细胞因子产生和免疫细胞迁移的影响。
反流性食管炎在术后第3天开始，黏膜下层出现淋巴细胞浸润，并进展至上皮表面——这些发现与腐蚀性化学损伤预期的情况相矛盾。基底细胞和乳头增生先于表面糜烂的出现。鳞状细胞暴露于酸化胆汁盐中显著增加了白细胞介素-8和白细胞介素-1β的分泌；这些细胞的条件培养基导致T细胞和中性粒细胞的迁移率显著增加。
这些发现支持但未证明反流性食管炎发展的另一种概念，即反流的胃液不会直接损伤食管，而是刺激食管上皮细胞分泌介导食管组织损伤的趋化因子。
