A NEW GASTRIC-ULCER MODEL INDUCED BY ISCHEMIA-REPERFUSION IN THE RAT - ROLE OF LEUKOCYTES ON ULCERATION IN RAT STOMACH

A new model of gastric ulcer involving damage to the muscularis mucosa e was developed by clamping the celiac artery in rat to induce ischemi a-reperfusion (I-R) injury. Although erosions with falling off of the gastric mucosa were observed immediately, 24 and 36 hours after the I- R, gastric ulcers involving the injury of muscularis mucosae were obse rved in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or p entoxifylline, an anti-leukocyte drug, just after the initiation of in jury significantly decreased the total area of ulcers at 72 hours. A c ombination of omeprazol and pentoxifylline was more effective than eit her drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibod y) also showed significant inhibitory effect on the development of ulc ers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid to gether with leukocytes contribute to the development of ulcers followi ng erosions. This model may be used to investigate the mechanisms of t he development of gastric ulcer and evaluate antiulcer drugs in a prec linical setting.