| Objectives: To observe the effect of Jia Jian SanJia San on the expression of MMP-1 and TIMP-1 in rats model of chronic atrophic gastritis,and to explore its therapeutic mechanism.Methods:60 SPF level Wistar male rats randomly divided into six groups :the normal group,the model group,Weimeisu treatment group,JiajianSanjia San high dose group,Jiajian Sanjia San middle dose group,Jiajian Sanjia San low dose group,with 10 rats for each group.Except the normal group,other groups freely drank 50ug/mL N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)solution,and were drunk with ranitidine hydroehloride at 0.03g/Kg one time a day,and were given two days to eat one day starved of irregular diet to construct the model of CAG,modeling for 60 days.After the animal was successfully produced by pathological examination,the treatment groups were given corresponding drugs once a day,the model group was given the same volume ofphysiologicalsaline,and the normal group was given the normal diet.After 12 weeks,all the animals were sacrificed and the gastric antrum was selected.The gastric antrum tissue was observed under light microscope and the expression of MMP-1 and TIMP-1 in gastric mucosa was observed by immunohistochemical method,then analysis the results.Results:1、general observation: rats of the normal control group were lively and actively,their weight increased gradually during the experiment,diet increased with weight gain.They also had closely and glossy hair.From the third week of the comprehensive building,the rats of rest groups gradually appear listlessness,activity decreased,lusterless hair,eating and drinking were reduced,some rats even had thin sloppy stool.At the end of modeling,the weight of model control group significantly reduced,activity reduced,hair became dry and rough,eating and drinking were reduced,too.Tenth days after intragastric administration,the above symptoms of each module gradually eased,the relieved degree(from small to large)as follows: WeiMeiSu treatment group,JiaJian SanJia San low dose group,high dose group,middle dose group;model group didn’t have obvious relief.2、Macroscopic observation: after dissection,we can observe as follows: normal control group of gastric mucosa in rats with smooth surface,is pink or reddish,mucosal folds neatly,muscle layer rich;model control group of gastric mucosa in rats with smooth surface,is dark red or pale,mucosal folds flat,reduced or even disappear,occasionally exposed or vascular lesion;The other treatment groups of rats gastric mucosa surface was smooth,slightly dark red,mucosal folds shallow I scattered bleeding points.3 、 HE staining observation :From the optical microscope,the animal gastric mucosa in normal group is regular,that is to say,defect and necrosis of gastric mucosa,gland atrophy,intestinal metaplasia,dysplasia couldn’t be observed.occasionally,a small amount of inflammatory cells,a normal phenomenon,could be observed.The model group could observe defective gastric mucosa,equirotal and disorder glands.We could find extensive thinning and atrophy glandular,even find ulcer lesions.The other treatment groups could observe little defective gastric mucosa,irregular glands.Some equirotal and atrophy glandular could be observed.occasionally,we could find a little gastric mucosal necrosis.There didn’t have any intestinal metaplasia or dysplasia.4 、Experimental study on the effect of JiaJianSanJia San on MMP-1 in rats model of chronic atrophic gastritis:The comparison of MMP-1 between the groups is significant.The expression of MMP-1 in model group is highest(P <0.05).The expression of Weimeisu group is higher than Jiajian Sanjia San high dose group、middle dose group and low dose group,and Jiajian Sanjia San middle dose group is lower than the Jiajian Sanjia san high dose and low dose group(P<0.05).5、Experimental study on the effect of JiaJianSanJia San on TIMP-1 in rats model of chronic atrophic gastritis:The comparison of TIMP-1 between the groups is significant.The expression of TIMP-1 in model group is lower than the normal group(P <0.05).The expression of TIMP-1in Weimeisu group is higher than the model group(P<0.05).The expression of Weimeisu group is lower than Jiajian Sanjia San high dose group、middle dose group and low dose group(P<0.05).There is no significant difference between the JiaJianSanJia San high group JiaJianSanJia San middle group and the JiaJianSanJia San low group(P >0.05).Conclusions:1.It can successfully created CAG model by using the integrated modeling method,with free drinking MNNG,integrate ranitidine and irregular diet.2.JiaJianSanJia San can improve the general situation and pathological changes in rat chronic atrophic gastritis models.3.JiaJianSanJia San can improve the expression of MMP-1 and depress the expression of TIMP-1 in CAG rat model,which might play a role in regulating expression mechanism between MMP-1 and TIMP-1,promoting the degrading and regenerating of ECM,enhancing the conversion of cell signal,in order to maintain the extracellular environment stability and regulate behavior of apoptosis,regeneration,differentiation,proliferation and senescence,so that the damaged gastric mucosa can repair,and ultimately resolve chronic atrophic gastritis.5.The experimental result shows that the clinical significance of JiaJianSanJia San is high and it provides a new gateway to the therapy of CAG. |
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