| Background:The incidence rate of chronic atrophic gastritis(CAG)in China is increasing,which has recognized as one of the difficult disease.If not controlled,it will develop for gastric cancer.Western medicine does not have an effective treatment of CAG,which could just relieve symptoms.The treatment of CAG in Chinese medicine is significantly effective,and has small side effects.Therefore,it is significant to develop the traditional Chinese medicine treatments on CAG.This study intends to make sure the molecular mechanism of the effect of Yiqi Huoxue Decoction in the treatment of CAG,through the Astragalus,Panax Notoginseng on CAG rat of hedgehog signaling pathway,to provide scientific basis for clinical application.Objective:To study the regulatory mechanism of Astragalus and Panax Notoginseng on apoptosis and Hedgehog signaling pathway in CAG rats;to investigate the effects ofAstragaloside Ⅳ and ginsenoside Rg1 on the regulation of Hedgehog signal pathway in CAG rats.Methods:Experiment one.Established two different CAG models in rats,one was induced by implantation of a pyloric spring and intragastic administration of hot starch paste with high-salt,the other was induced by MNNG.Compared the two models from pathological conditions,the level of serum gastrin,serum pepsinogen Ⅰ/Ⅱ and evaluated the characteristics of the two models.Experiment two.In the CAG model induced by implantation of a pyloric spring and intragastic administration of hot starch paste with high-salt,TUNEL was used to evaluate gastric mucosal cell apoptosis index and liquid phase chip to evaluate fas,fasl,EGF and TGF-β expression,to investigate the effect of Astragalus and Panax Notoginseng on atrophy gastritis rat apoptosis mechanism.Experiment three.In the CAG model induced by implantation of a pyloric spring and intragastic administration of hot starch paste with high-salt,tested the expression of Shh,PTCH,Gli 1/2/3 gene and protein expression,tested the Smo,SuFu,CyclinD1 protein by immunofluorescence detection,and compared the fluorescence intensity.Experiment four.Established the rat model of atrophic gastritis by MNNG,tested the expression of Shh,PTCH,Gli 1/2/3 gene and protein expression,tested the Smo,SuFu,CyclinD1 protein by immunofluorescence detection,and compared the fluorescence intensity.Experiment five.In the CAG model induced by implantation of a pyloric spring and intragastic administration of hot starch paste with high-salt,tested the expression of Shh,PTCH,Gli 1/2/3 gene and protein expression,SMO protein expression was tested by immunohistochemical.Sufu and cyclinD1 protein intensity were detected by immunofluorescence.In order to explore the regulation mechanism of hedgehog signal pathway of AstragalosideⅣand Ginsenoside Rgl in CAG rats.Results:1.The model established by Pylorus spring implantation with high salt hot starch paste showed inflammatory cell infiltration,lymphoid follicular formation.The model established by MNNG could lead to intestinal metaplasia.Compared with the control group,two models of serum gastrin hormone(GAS)were significantly reduced(P<0.05),PG I/PG Ⅱ level was reduced in MNNG group.(P<0.01).2.Compared with the blank group,the apoptosis index in Pylorus spring implantation preparation atrophy gastritis model decreased significantly(P<0.01).The expression of PCNA was significantly increased(P<0.01),serum levels of fas and fasL increased significantly(P<0.01),serum EGF level was significantly reduced(P<0.05).Compared with the model group,all the treatment groups can reduce the level of fas(p<0.05,p<0.01)Radix Astragali group and Radix Astragali,Radix Notoginseng group can significantly reduce the level of FasL(P<0.05),Astragalus and Panax notoginseng group can significantly elevated serum levels of TGF levels(P<0.05).3.Pylorus spring implantation induced atrophy gastritis rats model,Shh,Ptch,Gli-1 protein and gene expression were significantly lower(P<0.05,P<0.01)than the control group.In immunofluorescence test,SMO and cyclinD1 protein expression decreased significantly compared with the control group(P<0.01)and Sufu increased significantly(P<0.01).Compared with model group,the treatment groups could improved the expression of proteins and genes in different degree.Astragalus group and Astragalus Radix Notoginseng group were more effective(P<0.05,P<0.01).4.In the atrophy gastritis rat model established by MNNG,compared with the control group,Shh,PTCH,SMO and cyclinD1 protein expression were significantly decreased(P<0.05,P<0.01),Gli-2,Gli-3 and Sufu expression increased significantly(P<0.05,P<0.01);Compared with the model group,the treatment groups could improved the expression of proteins and genes in different degree,Panax Notoginseng group and Radix Astragali Radix Notoginseng group were more effective(P<0.05,P<0.01).5.Pylorus spring implantation induced atrophy gastritis rats model,ginsenoside Rg1 high dose group and low dose group could significantly improved Shh,PTCH protein expression,decreased the expression of Sufu,and the high dose group was more effective(P<0.05,P<0.01).Astragaloside high dose group could improve the expression of Gli-1 and increase cyclinDl protein expression(P<0.05).Conclusions:1.The CAG model reduced by pylorus spring implantation with high salt hot starch paste is given priority to inflammation,and the model reduced by MNNG compound multi factors appeared metaplasia of intestinal epithelium.2.Astragalus,Panax notoginseng and their compatibility can effectively inhibit the CAG rat gastric mucosal cell apoptosis and proliferation to protect the gastric mucosa.The effect of Astragalus and Panax notoginseng combined on apoptosis was obvious,and the effect of Astragalus on cell proliferation was significant.3.Astragalus,Panax notoginseng and their compatibility can activate the Hedgehog signal in CAG rats,the effect was significant for the upstream factor Shh and Ptch.The Astragalus group in improving mucosal atrophy and activation of hedgehog pathway was better than other traditional Chinese medicine group.4.Astragalus,Panax notoginseng and their combination can improve the gastric mucosal atrophy of CAG rats,the possible mechanism is to activate the Hedgehog signal.The curative effect of Panax notoginseng group was better than that of the other traditional Chinese medicine groups.5.Astragaloside,ginsenoside Rg1 can improve gastric mucosal pathology of CAG rats,the possible mechanism is to activate the Hedgehog signal,and then make the role of protection of gastric mucosa.The total effect is not as obvious as the traditional Chinese medicine Astragalus and Panax notoginseng. |
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