A novel gastric lesion model induced in rats by partial gastric vascular ligation.
Previous studies have suggested that histamine treatment after gastric vascular ligation induces mucosal damage in the rat stomach. Although ligation of left gastric artery and vein (L-AV) alone did not cause any damage in the stomach within 4 h, but provoked mild lesions due to ischaemia 24 h later. In the present study we demonstrated a new model of gastric lesions induced by L-AV ligation and examined the effects of various anti-ulcer drugs on this lesion model. The gastric lesions induced by L-AV ligation occurred at the corpus and antrum, especially at the corpus-antrum border, when examined 24 h later, and the severity of damage reached maximum 3 days after L-AV ligation. Repeated treatment with omeprazole or sucralfate for 3 days significantly prevented the development of gastric lesions induced by L-AV ligation, in whole mucosa, including the antrum. By contrast, famotidine given for 3 days showed a significant protection against total lesions in the whole mucosa, but had no effect on the antral lesions. Both omeprazole and famotidine dose-dependently decreased gastric acid output while sucralfate raised the intraluminal pH due to the acid-neutralizing action. These results suggest that the pathogenesis of gastric lesions induced by L-AV ligation differs depending on the region, the corpus and the antrum, and the lesions occurred in the latter area seem to be resistant to acid suppression. It is assumed that this new model of gastric lesions is useful for screening the drugs that affect gastric mucosal defense rather than acid secretion.
Kotani
Tohru
T
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Fujimura
Toshio
T
Amagase
Kikuko
K
Okabe
Susumu
S
Takeuchi
Koji
K
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000008:administration & dosage / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008026:Ligation / Q000009:adverse effects / Q000379:methods; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D013997:Time Factors
D000897:Anti-Ulcer Agents; D015738:Famotidine; D009853:Omeprazole