Effects of omeprazole on the esophageal mucosal cell proliferation and expressions of related genes in rats

doi:10.3969/j.issn.1002-7386.2014.22.003

Abstract：Objective To observe the effects of omeprazole on esophageal mucosal cell proliferation and expressions of related genes in rats with esophageal mucosal injury induced by reflux of acid.Methods Seventy-five healthy male SD rats,weighted 220~250g,were randomly divided into 5 groups: sham-operation group,model group ( simple gastroesophageal reflux model) ,omeprazole low-dose group,medium-dose group and high-dose group,with 15 rats in each group.The rat models of reflux esophagitis were induced by single acid reflux.The pathological changes of esophageal mucosal were examined by naked eye, HE staining and light microscopy.The expressions of p21, PCNA, CyclinD1 and CDK4 were detected by immunohistochemical staining,and the results were analyzed by HPIAS-1000 system.The data were statistically analyzed with SPSS10.0.Results The color of esophagus of rats was erythroid and lustrous, with glossy mucosal membranes in sham-operation group.As compared with that in sham-operation group,the esophagus presented light white and esophageal mucous membrane became rough, thickened, grey plaque-like proliferation in rats of model group.As compared with that in model group,the pathological changes of esophagus were significantly relieved in the three different doses omeprazole treatment groups ( P <0.05) .HE staining showed that the various layer structure of rat’ s esophagus was intact,the base membrane of mucosa was clear and cellular arrangement was orderly in sham-operation group.As compared with those in sham-operation group,the esophageal mucosa was thickened,the cell numbers were increased in basal cell layer and prickle cell layer,and the cuticulae layer was thickened and proliferated,with some mucosal tissue presenting nipple-like elevation in model group.As compared with those in model group,the pathological changes of esophageal mucosa were significantly alleviated in omeprazole treatment groups ( P <0.05 ) .The results by immunohistochemistry showed that there was positive expression of p21 and basic expression of PCNA, CyclinD1 and CDK4 in basal cell layer of esophageal mucous membrane in sham-operation group. However the expression of p21 was decreased,the expressions of PCNA,CyclinD1,CDK4 were significantly increased in model group ( P <0.05).As compared with those in model group,the expression of p21 was increased,and the expressions of PCNA,CyclinD1,CDK4 were significantly decreased in omeprazole treatment groups ( P <0.05).Conclusion Omeprazole can up-regulate the expression of p21 after reflux esophagus injury and down-regulate the expressions of PCNA,CyclinD1 and CDK4,moreover,its inhibition effect on cell proliferation may be important action mechanism in treatment of reflux esophagus injury.