Gastroprotective Effect Of Rosiglitazon On Alcohol-induced Acute Gastric Mucosal Lesions

OBJIECTIVE This study was designed to determine the protective effect of rosiglitazon, a specific ligand for peroxisome proliferators activated receptor gamma (PPAR-γ), on gastric mucosal lesions induced in rats by alcohol administration and it relation to cyclooxygenase-2 (COX-2).METHOD 50 healthy Male S-D rats were employed in the study and divided into 5 groups randomly according to weight. The rats fasted for 24h before the study, rats received pretreatment: normal control group and injury model group (saline 5ml/kg i.g.); omeprazol group(Omeprazol 30 mg/kg i.v.);rosiglitazon group(rosiglitazon 8 mg/kg i.g.); co-treatment group (rosiglitazon 8 mg/kg i.g. and Omeprazol 30 mg/kg i.v.) respectively . After 0.5 h ,all the animals except normal control group were given administration of 56°Hongxing Erguotou wine(18ml/kg).The same treatment was carried out on normal control group except that physiological saline was applied instead . Rats were killed six hours after alcohol administration.. The index of gastric mucosal injury was evaluated macroscopically according to Guth's method . Gastric mucosa structural changes were abserved under the microscope .Immuno- histochemistry was used to examine the mucosal expression of COX-2 protein.RESULTS 1.Model of the acute gastric injury in rats induced by alcohol was set up successfully. 2.The pathological changes of gastric mucosa which exposed alcohol were significant. Erosion ,bleeding and necrosis of gastric mucosa were observed.The most severe gastric mucosal injury was found in model group, then in rosiglitazon group, the rats in Omeprazol group were found with the a thirdly mucosal injury, next lesion degree was in co-treatment group .The mildest gastric mucosal injury was found in normal control group,there had statistical significance between each group (P<0.05) 3. Pathologic changes with HE dyeing: No histological damage was observed in the gastric mucosa of normal group ; exfoliation and necrosis of superficial cells, structural alterations on the glandular pits, and bleeding erosions developed in all stomachs. The architecture of the crypts was distorted, and an infiltrate consisting of polymorphonuclear leukocytes, lymphocytes was observed.Pretreatment with rosiglitazone or (and)Omeprazol produced different degree reduction of exfoliation of superficial cells, haemorrhage, and blood cell infiltration. The recuperation of the typical structure and alignment of the gastric gland mucosa was also observable. 4. Cyclooxygenase-2 was scarcely found in mucosa of the normal group, although it was clearly present in the injury model group after alcohol i.g. where COX-2 was detected in mucous surface cells and mucous cells of the foveoles adjacent to the ulcer crater, the expression of COX-2 in the injury model group was significantly higer than normal group (P<0.05) . The expression of COX-2 in Omeprazol group was no different to the ulcerated control (P> 0.05). The expression of COX-2 Rosiglitazone and co-treatment group were lower than injury model group (P<0.05) , and there were no different between the two group (P> 0.05) .CONLCUSION1 Omeprazole plays an important protective role in the gastric mucosa in rats, which COX-2 is not involved in.2. Rosiglitazone reduces the damage in acute gastric injury induced by alcohol.3.Co-treatment with omeprazole and rosiglitazone seem to contribute significantly to the gastroprotection in this experimental model.4.The beneficial effects of rosiglitazone on alcohol-induced gastric mucosal injury may be attributed to down-regulation of proinflammatory cytokines.