Imamoto Haruhiko, Hashimoto Naoki, Shiozaki Hitoshi
Department of Surgery, Kinki University, Osaka, Japan.
Hepatogastroenterology. 2011 Sep-Oct;58(110-111):1574-9. doi: 10.5754/hge10829. Epub 2011 Jul 15.
BACKGROUND/AIMS: Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The aim is to clarify the effect of PPI (rabeparazole) on these factors in esophagitis.
Sixteen 8-week old male Wistar rats underwent total gastrectomy and esophagoduodenostomy to induce esophageal reflux of duodenal juice. In 5 rats, the sham operation induced a midline laparotomy alone. One week following surgery, they were treated with control (saline) or PPI (rabeprazole) (30mg/kg) ip. Three weeks after operation, all rats were euthanized and the esophagus was evaluated histologically. Esophageal injury was evaluated by macroscopic and microscopic findings, and expression of COX2 and PGE2. Esophageal washing was aspirated for the evaluation of bile acid activity.
At 3 weeks after surgery, duodenal reflux induced esophageal erosions and ulcer formation as well as marked thickening of esophageal wall. The macroscopic ulcer score and histological ulcer length were significantly reduced by treatment with rabeprazole. The enhanced expression of COX2 and PGE2 in the control group was also markedly inhibited in the rabeprazole treated group. The bile acid activity in the esophageal lumen was significantly increased in the control group and this increase was significantly inhibited in the rabeprazole treated group.
Rabeprazole significantly reduces inflammation and hyperplasia in esophageal mucosa. These results indicate that bile acid, inhibited by rabeprazole, plays an important role in mucosal damage induced by duodenal reflux.
背景/目的:全胃切除术后食管炎与胆汁和胰液反流至食管有关。目的是阐明质子泵抑制剂(雷贝拉唑)对食管炎这些因素的影响。
16只8周龄雄性Wistar大鼠接受全胃切除术和食管十二指肠吻合术以诱导十二指肠液反流至食管。5只大鼠仅接受假手术,即正中剖腹术。术后1周,它们分别接受腹腔注射对照剂(生理盐水)或质子泵抑制剂(雷贝拉唑)(30mg/kg)治疗。术后3周,所有大鼠均安乐死,对食管进行组织学评估。通过宏观和微观检查结果以及COX2和PGE2的表达评估食管损伤情况。抽取食管冲洗液以评估胆汁酸活性。
术后3周,十二指肠反流导致食管糜烂和溃疡形成以及食管壁明显增厚。雷贝拉唑治疗可显著降低宏观溃疡评分和组织学溃疡长度。雷贝拉唑治疗组也显著抑制了对照组中COX2和PGE2表达的增强。对照组食管腔内胆汁酸活性显著增加,而雷贝拉唑治疗组可显著抑制这种增加。
雷贝拉唑可显著减轻食管黏膜的炎症和增生。这些结果表明,雷贝拉唑抑制的胆汁酸在十二指肠反流诱导的黏膜损伤中起重要作用。