Hayakawa T, Fujiwara Y, Hamaguchi M, Sugawa T, Okuyama M, Sasaki E, Watanabe T, Tominaga K, Oshitani N, Higuchi K, Arakawa T
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abenoku, Osaka 545-8585, Japan.
Gut. 2006 Apr;55(4):450-6. doi: 10.1136/gut.2005.081943. Epub 2005 Oct 6.
Although prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), and microsomal prostaglandin E synthase 1 (mPGES-1) are known to play a role in various inflammatory events, their roles in the pathogenesis of gastro-oesophageal reflux disease are not known.
We examined the dynamics of COX-1, COX-2, mPGES-1, mPGES-2, cytosolic PGES (cPGES), and PGE2 synthetic activity in rat acid reflux oesophagitis and the effects of COX-2 inhibitors on the severity of oesophagitis.
Acid reflux oesophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus. Rats were killed on day 3 (acute phase) or day 21 (chronic phase) after induction of oesophagitis.
Expression of COX-2 and mPGES-1 was markedly increased in oesophagitis while modest changes in COX-1, cPGES, and mPGES-2 expression were observed. COX-2 and mPGES-1 were colocalised in epithelial cells of the basal layer, as well as inflammatory and mesenchymal cells in the lamina propria and submucosa. COX-2 inhibitors significantly reduced the severity of chronic oesophagitis but did not affect acute oesophageal lesions. COX-2 inhibitors significantly inhibited the increase in PGE2 synthesis in oesophageal lesions on both days 3 and 21. Epithelial proliferation was significantly increased in the basal layer on day 21. Inflammatory cells and epithelial cells of the basal layer exhibited reactions for EP4 in oesophagitis.
PGE2 derived from COX-2 and mPGES-1 plays a significant role in the pathogenesis of chronic acid reflux oesophagitis, and possibly in basal hyperplasia and persistent inflammatory cell infiltration.
尽管已知前列腺素E2（PGE2）、环氧化酶2（COX-2）和微粒体前列腺素E合酶1（mPGES-1）在各种炎症事件中发挥作用，但其在胃食管反流病发病机制中的作用尚不清楚。
我们研究了大鼠酸反流性食管炎中COX-1、COX-2、mPGES-1、mPGES-2、胞质型PGES（cPGES）和PGE2合成活性的动态变化，以及COX-2抑制剂对食管炎严重程度的影响。
通过结扎前胃和腺胃之间的过渡区域并包裹幽门附近的十二指肠来诱导酸反流性食管炎。在诱导食管炎后第3天（急性期）或第21天（慢性期）处死大鼠。
食管炎中COX-2和mPGES-1的表达显著增加，而COX-1、cPGES和mPGES-2的表达有适度变化。COX-2和mPGES-1共定位于基底层的上皮细胞以及固有层和黏膜下层的炎症细胞和间充质细胞。COX-2抑制剂显著降低了慢性食管炎的严重程度，但不影响急性食管病变。COX-2抑制剂在第3天和第21天都显著抑制了食管病变中PGE2合成的增加。第21天基底层的上皮增殖显著增加。食管炎中基底层的炎症细胞和上皮细胞对EP4有反应。
源自COX-2和mPGES-1的PGE2在慢性酸反流性食管炎的发病机制中起重要作用，可能在基底增生和持续性炎症细胞浸润中起作用。
