Effects of cyclooxygenase-2 inhibitors on the healing of gastric mucosal damage in rats / 中华消化杂志

ABSTRACT

Objective Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins (PGs), exists in two isoforms (COX 1 and COX 2). Conventional non steroidal anti inflammatory drugs (NSAIDs) inhibit both COX 1 and COX 2 activities and induce serious gastrointestinal side effects. Specific COX 2 inhibitors are expected to cause fewer gastric side effects. The aim of this study was to investigate the effects of specific and non specific COX 2 inhibitors on gastric wound healing following acid induced injury. Methods Male Sprague Dawley rats were given 1 ml of 0.6 mol/L hydrochloric acid (HCl) into the stomach. Levels of COX 1 and COX 2 in gastric mucosa were analyzed using western blotting and immunohistochemical staining. At 10 minutes after the administration of the acid, the animals were given 0.4, 4 and 40 mg/kg of NS 398 (NS) or 40 mg/kg of indomethacin (IM). Control group was given 1% arabic gum (AG) in a volume of 5 ml/kg. The rats were sacrificed and laparotomized before and at 1, 3, 6, 12, 24, 48 h after acid administration. Lesion index (LI) was measured and morphological changes of gastric mucosa were assessed under light microscopy. Results Expression of COX 2 was enhanced mainly in surface epithelial cells and neck cells after HCl administration. NS and IM delayed the healing of gastric injury. At 12 h after acid administration, LI was (1.42 ? 0.23)% and (1.42 ? 0.29)% in the groups treated with 4 and 40 mg/kg of NS respectively, and (1.62 ? 0.44)% in the group treated with 40 mg/kg of IM, which was significantly higher than that in control group [(0.58?0.24)%, P