The study on the protection of proton pump inhibitors in diclofenac induced small intestinal injury / 中华消化杂志

ABSTRACT

ObjectiveTo explore the protective effects and possible mechanism of different type of proton pump inhibitors (PPIs) in non-steroid anti-inflammatory drugs (NSAIDs)induced small intestinal injury.MethodsSeventy two SD rats were randomly and equally divided into control group,model group,Omeprazole treated group,Esomeprazole treated group,Rabeprazole treated group and Lansoprazole treated group.Except control group,rats of other groups were gavaged with diclofenac 7.5 mg · kg-1 · d-1,once daily to make NSAIDs related small intestinal injury model.The treated groups were gavaged with Omeprazole 30 mg · kg1· d-1,Esomeprazole 30 mg· kg1 · d-l,Lansoprazole 45 mg · kg1 · d-1 and Rabeprazole 15 mg · kg-1 · d-1 once daily respectively.Continuous administration for five days and then executed,small intestinal tissues were taken and observed for gross and pathological changes.The expression level of nuclear factor erythroid-2-related factor 2(Nrf2) at protein and mRNA level were detected with western blot and real time PCR assay.The qualitative and location of Nrf2 in small intestinal tissue were analyzed by immunohistochemistry staining and the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) in small intestinal tissue were determined with xanthine oxidase method and TBA respectively.ResultsThe successful rate of modeling experiment was 100％.The survival ratio of control group rats,model group,Omeprazole treated group,Esomeprazole treated group,Rabeprazole treated group and Lansoprazole treated group was 12/12,3/12,2/12,1/12,1/12 and 2/12 respectively.The tissue injure scores of Esomeprazole treated group,Rabeprazole treated group and Lansoprazole treated group were significantly lower than that of model group (P＜0.05).The activity of SOD in small intestinal of Rabeprazole treated group was obviously higher than that of model group (P＜ 0.05),while the activity of MDA in Rabeprazole and Esomeprazole treated groups were significantly lower than that of model group (P＜0.05).The results of westen blot indicated that the expression of Nrf2in small intestinal tissue was obviously higher in Rabeprazole treated group than in model group (P＜0.05).The real time PCR results suggested that the expression of Nrf2 at mRNA level in small intestinal tissue of Rabeprazole treated group was obviously higher than those of model and control groups (P＜0.05).Conclusions The protection effects of various PPIs are different in NSAIDs related intestinal injury.There is no obvious protection effect of Omeprazole.Rabeprazole may prevent NSAIDs related intestinal injury by up-regulating expression of Nrf2 and promoting its activation.