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Objective To investigate the effect and the mechanisms of astragalus polysaccharides (APS) on chronic atrophic gastritis (CAG) induced by MNNG in rats.Method Seventy rats were randomly divided into six groups:group Ⅰ (control),group Ⅱ (CAG model),group Ⅲ (APS 1g/kg),group Ⅳ (APS 0.5g/kg),group Ⅴ (RA 0.01g/kg),and group Ⅵ (FA 0.01g/kg).Group Ⅰ served as the control group and the five experimental groups were administered MNNG (1.7mg/kg) and also allowed 150μg/ml MNNG water stored in black bottles ad libitum everyday for 12 weeks.As promoting agents,rats were also given 40% alcohol (1ml/100g) twice a week and irregular diet with fasting or repletion intervals.From the 5th week group Ⅲ,group Ⅳ,group Ⅴ,and group Ⅵ were daily given 1g/kg APS,0.5g/kg APS,0.01g/kg RA and 0.01g/kg FA respectively.Rats were checked daily for body weight,behavior arnd food consumption.The experiment was finished at the end of 12 weeks,serum or plasma collected,stomach was removed for HE stain.The expression of cyclooxgenase-2 (cox-2),matrix metallo proteinase-2 (MMP-2) and epithelium growth factor receptor (EGFR) level in gastric tissue were measured by immunohistochemical method.Plasma gastrin,motilin and somatostatin were measured by radioimmunoassay method.Prostaglandins E2 (PGE2) level in stomach tissue homogenate were measured by UV spectrophotometry.Serum secretary immunoglobulin A (SIgA),GSH,and GSSG were measured using Elisa kits.Results In rats in which CAG had been induced; body weights were approximately 2-fold lower at the 12th week than control.Obvious pathological changes were found with gastric mucosa epithelial degeneration,lamina propria lymphocyte or plasma cell infiltration,local mucosal erosions,and superficial ulcer formation.Gastrointestinal hormone levels changed that plasma gastrin,somatostatin and serum sIgA decreased while plasma motilin and tissue PGE2 level increased significantly compared with control.Immunohistochemistry detection showed that cox-2,EGFR,and MMP-2 high expression in CAG rats gastric tissue.The general index and severe morphology changes of CAG rats were improved by administrated APS.APS increased the plasma gastrin and somatostatin level significantly but had no significant effect on motilin level.Data demonstrated APS could raise serum sIgA level distinctly and obviously decrease the expression of cox-2 and tissue PGE2 level.Conclusions In the present study,a stable MNNG-induced CAG rats model using alcohol and irregular diet as promoting agents was established.Based on the model,general index improvement,morphology improvement and plasma hormone rejuvenation indicated that Astraglus polysaccharide (APS) had good effect on CAG treatment.This study also suggests that APS remedy CAG by both reversing the imbalance of protective sIgA and deregulating EGFR and its downstream MMP-2 and cox-2/PGE2.