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 mucosae was developed by clamping the celiac artery in rat to induce ischemia-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 observed in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or pentoxifylline, an anti-leukocyte drug, just after the initiation of injury significantly decreased the total area of ulcers at 72 hours. A combination of omeprazol and pentoxifylline was more effective than either drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibody) also showed significant inhibitory effect on the development of ulcers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid together with leukocytes contribute to the development of ulcers following erosions. This model may be used to investigate the mechanisms of the development of gastric ulcer and evaluate antiulcer drugs in a preclinical setting.
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan. wadakou@grape.med.tottori-u.ac.jp
K
K
Wada
Y
Y
Kamisaki
M
M
Kitano
Y
Y
Kishimoto
K
K
Nakamoto
T
T
Itoh
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000502:physiology; D005753:Gastric Mucosa / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*; D013276:Stomach Ulcer / Q000188:drug therapy / Q000473:pathology*
D000897:Anti-Ulcer Agents; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D010726:Phosphodiesterase Inhibitors; D009853:Omeprazole; D010431:Pentoxifylline