| Chronic atrophic gastritis(CAG)is a chronic stomach disease characterized by a decrease or disappearance of the number of glands in the gastric mucosa,with or without fibrosis,intestinal gland metaplasia,or pseudopyloric gland metaplasia.The incidence of CAG increases with age,moreover,CAG is also closely related to the occurrence of gastric cancer,and the annual cancer rate of CAG is 0.15%-1%.With the changes in modern people's living habits,the incidence of this disease is increasing year by year,and the trend of young age is more and more obvious.Because the incidence of this disease is high,and it is often recurrent in clinical practice,it is not easy to cure,and it is closely related to the occurrence of gastric cancer.Therefore,the treatment of CAG has gained more and more attention.The purpose of this study was to investigate the pharmacodynamic effects and the mechanisms of how it effects.1 Therapeutic effect of Weikangning Granule on CAG model ratsObjective:To study the therapeutic effects of Weikangning Granule on gastric mucosa of CAG model rats,and then provide the basis experimental data for its clinical curative and new drug application,we observed the effects of Weikangning Granule on the weight,food intake,gastric secretion function of CAG model rats and the pathological examination of gastric mucosa.Method:In this experiment,the rats were given free to drink 120?mol/L MNNG solution and stimulated with ranitidine,ethanol and hunger-saturated 26w to replicate CAG model rats.The weight,food intake and water intake of each group were monitored weekly.Rats were randomly selected,stomach were taken,and histopathological staining was used to determine whether the model was replicated successfully.After successful modeling,the rats were randomly divided into 6 groups according to weight:control group,three dosage groups of Weikangning granules with high(29.800g/kg),medium(14.900g/kg)and low(7.450g/kg),the positive drug folic acid group(0.002g/kg)and the Moluodan group(0.828g/kg),setting the normal group from the beginning of the experiment.Intragastric administration of appropriate drugs,and the weight,food intake and water intake of each group were monitored weekly.Eight weeks after intragastric administration,the gastric tissue was routinely stained with HE,and the degree of gastric mucosal inflammation and atrophy were scored.The number of glands in the range of 1 mm of gastric antrum was counted,and the thickness of gastric mucosa and mucosal muscle layer were measured.The ratio of Gastric mucosal thickness(L2)/mucosal muscle thickness(L1)was calculate.The gastric secretion function,gastric acidity and pepsin activity were measured in each group.Result:During the modeling and administration,the weight and water consumption of the control group was smaller than those of the normal group.Eight weeks after intragastric administration,compared with the control group,there were no significant difference in weight and food intake among the rats with each medication.The pathological results showed that compared with the normal group,the degree of inflammatoryness of the control group was significantly increased(P<0.01)Eight weeks after intragastric administration,compared with the control group,the degree of gastric mucosal inflammation was significantly decreased in the high-dose group of Weikangning granules(P<0.05);Compared with the normal group,the degree of atrophy in the control group was significantly increased(P<0.01).Eight weeks after intragastric administration,compared with the model group,the gastric mucosal atrophy of the high-and low-dose group of Weikangning granules,the folic acid group and the Molodan group were decreased(P<0.05).Compared with the normal group,the mucosal thickness of the control group became thinner and the thickness of the mucosal muscle layer became thicker.The ratio of the two groups and the number of glands in the control group were significantly decreased(P<0.01).Eight weeks after intragastric administration,the gastric mucosal thickness of each medication rats groups were thickened to varying degrees,mucosal muscle layer thickness were thinned to varying degrees.Compared with the control group,the ratio of gastric mucosal thickness/mucosal myometrial thickness were significantly increased(P<0.05 or P<0.01),and the number of glands in each medication rats group were increased(P<0.05 or P<0.01).Compared with the normal group,the gastric juice secretion of the control group were significantly decreased(P<0.01).Compared with the control group,the gastric juice secretion in the medium-dose group of Weikangning granules was increased significantly(P<0.05).Compared with the normal group,the gastric acidity of the control group was significantly decreased(P<0.01).Compared with the control group,the gastric acidity of the high-dose group and the folic acid group were increased in different degrees(P<0.05 or P<0.01).Compared with the normal group,the pepsin activity of the control group was significantly decreased(P<0.01),and the pepsin activity of Weikangning high dose group,Weikangning low dose group and folic acid group were significantly increased(P<0.01).Conclusion:Weikangning granules could significantly improve gastric mucosal lesions,reduce the thickness of the mucosal muscle layer,increase the gastric mucosal thickness,the number of glands,and the ratio of gastric mucosal thickness to mucosal muscle thickness,inhibit the gastric mucosal atrophy in CAG model rats induced by MNNG and other factors.Weikangning granules also could increase gastric juice secretion,gastric acidity,and increase pepsin activity in CAG model rats.It suggested that Weikangning granule might have theapeutic effect on CAG model rat.2 Study on the Mechanism of Weikangning Granules in CAG Model Rats2.1 Effect of Weikangning Granule on the expression of Proteins associated to Gastric Mucosal Epithelial Proliferation in CAG Model RatsObjective:In this experiment,the experimental CAG model rats were induced with MNNG simultaneous,ranitidine,ethanol stimulation,hunger and satiety and other factors.To observe the protective mechanism of Weikangning Granule on gastric tissue of CAG rats,the protein expression of epidermal growth factor(EGF),vascular endothelial growth factor(VEGF),epidermal growth factor receptor(EGFR)and proliferating cell nuclear antigen(PCNA)in gastric tissue of CAG model rats were observed.Method:The preparation and grouping method of experimental animal models were the same as the first part.The protein expression of EGF,VEGF,EGFR and PCNA in gastric tissues were determined by immunohistochemistry.Result:Eight weeks after intragastric administration,the protein expression of EGF,VEGF,EGFR and PCNA in the control groups were significantly higher than that in the normal group(P<0.05 or P<0.01).Compared with the control group,the expression of PCNA in the folic acid group,the high-dose group,the low-dose group,and the moluodan group were significantly decreased(P<0.05).The expression of EGF in the high dose group was significantly decreased(P<0.05).The expression of EGFR in the folic acid group and the high dose group were significantly decreased(P<0.05 or P<0.01).The expression of VEGF in the folic acid group and the high dose group were significantly decreased(P<0.05).Conclusion:Regulating the protein expression of EGF,VEGF,EGFR and PCNA minght be included in the mechanism of Weikangning Granules in CAG model rats.2.2 Effect of Weikangning Granule on oxidative stress response,gastrointestinal hormone and cytokines in CAG Model RatsObjective:In this experiment,the experimental CAG model rats wasse induced with MNNG simultaneous,ranitidine,ethanol stimulation,hunger and satiety and other factors.Through the therapeutic effects of oxidative stress,gastrointestinal hormones and cytokines in CAG model rats,the mechanism of Weikangning granules in the treatment of CAG model rats was investigated,and the effect of Weikangning granules on chronic atrophy were further verified.Method:The preparation and grouping method of experimental animal models were the same as the first part.The content or activity of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)in serum and gastric mucosa homogenate were detected by colorimetry.Determination of gut hormones and cytokines by serum enzyme-linked immunosorbent assay(Elisa),such as motilin(MTL),gastrin(GAS),vasoactive intestinal peptide(VIP),and pepsinogen ?(PGI),pepsinogen ?(PGII),epidermal growth factor(EGF),and prostaglandin E2(PGE2)Result:Compared with the normal group,the serum SOD and GSH-Px activities were significantly decreased in the control group(P<0.01),and the serum MDA concentration was significantly increased in the control group(P<0.01).Compared with the control group,each medication group could increase the activity of SOD and GSH-Px in serum(P<0.05 or P<0.01).The high-dose group,middle-dose group,folic acid group and moluodan group could reduce serum MDA content(P<0.05 or P<0.01).Compared with the normal group,the activity of SOD and GSH-Px in the gastric mucosa of the control group were significantly decreased(P<0.05),and the concentration of MDA in the tissue homogenate was significantly increased(P<0.01).Compared with the control group,the medium-dose group of Weikangning granules and the folic acid group could increase the activity of SOD in tissue homogenate(P<0.05 or P<0.01).The high dose group of Weikangning Granules,the low dose group of Weikangning Granules and the folic acid group could increase the activity of GSH-Px in tissue homogenate(P<0.05 or P<0.01).The high dose group of Weikangning Granules,the medium-dose group of Weikangning Granules,the low dose group of Weikangning Granules and the folic acid group could reduce the concentration of MDA of tissue homogenate(P<0.05 or P<0.01).Th ere were no significant effect on serum PGII,GAS and PGE2 levels in each medication group,but the concentration of PGII,GAS and PGE2 in each medication group were increased.Compared with the normal group,the concentration was decreased of serum PGI(P<0.01).Compared with the control group,serum PGI level was increased in different dose groups(P<0.05 or P<0.01).Compared with the normal group,the serum EGF concentration was significantly increased(P<0.01).Compared with the control group,the high dose group and the medium dose group of Weikangning granules were significantly decreased of the EGF concentration(P<0.05).Compared with the normal group,serum VIP and MTL levels were increased(P<0.05 or P<0.01).Compared with the control group,serum VIP and MTL levels were decreased in different dose groups(P<0.05 or P<0.01).Conclusion:Weikangning granules may be used to treat CAG model rats by regulating the levels of SOD,MDA and GSH-Px in serum and tissues and the levels of MTL,PGI,EGF and VIP in serum.In summary,Weikangning granules could promote the secretion of gastric juice in CAG model rats,and repair the damaged gastric mucosa.Weikangning granules could regulate the expressions of gastric mucosal injury repair related proteins,and prevented CAG from further developing towards gastric cancer.Weikangning granules could regulate the balance of oxidative stress in CAG model rats,and effectively protected the gastric mucosa of CAG model rats.Weikangning Granules had a certain regulation effect on the concentration of serum gastrointestinal hormones and cytokines. |
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