Kanazawa Yusei, Isomoto Hajime, Wen Chun-Yang, Wang Ai-Ping, Saenko Vladimir A, Ohtsuru Akira, Takeshima Fuminao, Omagari Katsuhisa, Mizuta Yohei, Murata Ikuo, Yamashita Shunichi, Kohno Shigeru
Second Department of Internal Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan.
World J Gastroenterol. 2003 Dec;9(12):2801-4. doi: 10.3748/wjg.v9.i12.2801.
Little has been known about the pathogenesis of non-erosive reflux disease (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development and progression of gastroesophogeal reflux disease (GERD). The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes.
We studied 26 patients with NERD and 13 asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction (PCR). We also examined mRNA expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The patients were endoscopically classified into grade M (mucosal color changes without visible mucosal break) and N (neither minimal involvement nor mucosal break) of the modified Los Angeles classification.
The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls. There was a significant difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa.
Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.
关于非糜烂性反流病（NERD）的发病机制，人们了解甚少。最近的研究表明白细胞介素8（IL-8）与胃食管反流病（GERD）的发生和发展有关。本研究的目的是确定有无细微黏膜改变的NERD患者中IL-8 RNA的表达水平。
我们研究了26例NERD患者和13例无症状对照者。从胃食管交界处上方3 cm处的食管取活检样本，速冻后通过实时定量聚合酶链反应（PCR）测量IL-8 mRNA水平。我们还通过逆转录PCR检测了IL-8受体CXCR-1和-2的mRNA表达。患者在内镜检查中根据改良的洛杉矶分类法分为M级（黏膜颜色改变但无可见黏膜破损）和N级（无最小程度累及且无黏膜破损）。
NERD患者食管黏膜中IL-8 mRNA的相对表达水平显著高于对照组食管黏膜中的水平。M级和N级之间的IL-8 mRNA水平存在显著差异。CXCR-1和-2 mRNA在食管黏膜中组成性表达。
我们的结果表明，食管黏膜中高IL-8水平可能通过与其受体相互作用参与NERD的发病机制。NERD似乎不仅在镜下最小程度累及方面，而且在免疫和炎症过程方面都由异质性人群组成。
