The Expression And Significance Of NF-κB, IκB And Ubiquitin In Rats With Chronic Atrophic Gastritis

Objective and Background:Chronic atrophic gastritis (CAG) is a common and long course disease of digestive system. CAG especially accompanied with intestinal metaplasia or dysplasia is considered as precancerous lesion which is a critical threat to mankind. CAG is an important stage of disease in the sequence of normal epithelium→chronic Inflammation→atrophy→metaplasia→dysplasia→cancer and there is still an argument on whether CAG is a curable disease. To explore the molecular pathogenesis mechanisms of CAG and to control its progress become very significant. NF-κB has been the focus of intense investigation in recent years. Research results show that NF-κB plays a central role in inflammation and acts as a critical mediator of cancerization progress. NF-κB has been an important target of adjunctive therapy for autoimmune disease, inflammation and cancer. Our clinical research results have showed that NF-κB was activated obviously in gastric cancer. Therefore, exploration of expression and role of NF-κB in CAG is practical for the therapy of the disease and prevention of gastric cancer. The aim of this study was to establish a new animal model of CAG, to examine the expression of NF-κB, IκB and Ubiquitin and to study the role of NF-κB signaling pathway in CAG development.Materials and Methods:CAG experimental model in male Wistar rats was established. 30 rats were randomly divided into the control group (10) and the model group (20). 50℃20mmol/L sodium deoxycholate, 60% alcohol and 0.05% ammonia water were given in combination to rats in model group for 6 months. Pathologic diagnosis of CAG was confirmed through light microscopy and scanning electron microscopy. The expression of NF-κB, IκB and Ubiquitin were assessed by immunohistochemistry and Western blotting assay. Then the relationships between the factors and the severity of gastritis were approached. Results:1. A new CAG model was successfully established in rats by multiple factors for 6 months. Compared with the control group, the body weight of rats decreased obviously, atrophy of glands and notable inflammatory infiltration were observed in model group. The incidence of intestinal metaplasia and dysplasia in model group was 44.4% and 22.2% respectively. The successful rate of CAG was 100.0%.2. Compared with the control group, expression of NF-κB and Ubiquitin in model group increased obviously (P＜0.05), whereas the expression of IκB reduced significantly (P＜0.05).3. The expression level of NF-κB and Ubiquitin was positively correlated to the severity of gastritis (r=0.693, r=0.695, P＜0.01, respectively). However, IκB was negatively correlated to the severity of gastritis (r= -0.674, P＜0.01).Conclusions:1. A new CAG model was successfully established in Wistar rats by multiple factors for 6 months. Precancerous lesions occurred in some of the rats.2. NF-κB signaling pathway was activated in gastric mucosa of CAG rats.3. Activation of NF-κB signaling pathway revealed positive correlation to the severity of gastritis.4. Persistent activation of NF-κB signaling pathway and the increase of nuclear translocation accompanied with the severity of gastritis suggested that the inhibition of NF-κB activation may be one of the methods for therapeutic intervention in CAG.