Protective Effect Of Rabamipide On Non-steroid Anti-inflammatory Drugs Induced Intestinal Injury In Rats

Objective:To investigate the effect of rabamipide on non-steroid anti-inflammatory drugs (NSAIDs) induced intestinal injury in rats and the possible mechanisms.Methods:Thirty male Sprague Dawley rats were divided into three groups randomly: control group; diclofenac induced injury group; rabamipide pretreatment group. Intestinal injury was induced in rats of diclofenac induced injury group and rabamipide pretreatment group by intragastric administration of diclofenac (7.5 mg/kg) once per day with a continuous of 4 days. Rabamipide pretreatment group was pretreated with rabamipide (100 mg/kg) orally once daily 1 h before the administration of diclofenac. The control group received the same amount of 0.9% NaCl by gavage during the same period. All the rats were sacrificed on the 5th day. Small intestinal injuries were assessed for histopathological damage as well as macroscopic injury and recorded as corresponding scores respectively. Immunohistochemistry and Western blot assay were used to detect the distribution and expression of intestinal epithelial tight junction protein Occludin. The expression of ERK, p-38, JNK and phosphorylation-ERK (p-ERK), phosphorylation-p38 (p-p38) as well as phosphorylation-JNK (p-JNK) were determined by Western blot.Results:Compared with the control group, histopathological and macroscopic scores of intestinal damage of rats were significantly increased in diclofenac induced injury group (P< 0.05). While intestinal damage scores of rats in rabamipide pretreatment group were significantly decreased compared with that in diclofenac group (P< 0.05). Compared with control group, expression of Occludin protein in diclofenac group was decreased significantly (P< 0.05), while that of rabamipide pretreatment group increased significantly compared with that in diclofenac group (P < 0.05). Significant activation of ERK and p38 were seen in diclofenac group compared with control group (P< 0.05), and pretreatment with rabamipide could inhibit the activation of both ERK and p38 significantly compared with that in diclofenac group (P< 0.05). However, the expression of p-JNK was not significantly different in neither two of the three groups.Conclusion:Rabamipide exerts a protective effect on NSAIDs induced intestinal injury in rats, probably via the inhibition of activation of both ERK and p38 signaling pathways as well as the increase in the expression of Occludin protein, thus collectively restore the intestinal mucosa barrier.