Objective To investigate the effect of modified Leweiyin Formula(MLF)on key glycolytic regulatory targets in the gastric mucosa of rats with chronic atrophic gastritis(CAG)based on the phosphatidylinositol 3-kinase(PI...Objective To investigate the effect of modified Leweiyin Formula(MLF)on key glycolytic regulatory targets in the gastric mucosa of rats with chronic atrophic gastritis(CAG)based on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signalingpathway.Methods The CAG rat model was induced using a combination of free drinking of 1-methyl-3-nitro-1-nitrosoguanidine(MNNG),oral administration of sodium salicylate,and an irregular feeding schedule.After modeling,except for the blank group,the remaining rats were randomly divided into the model group,Vitacoenzyme group,Chinese medicine(CM)low-dose group(6.3 g/kg),and CM high-dose group(25.2 g/kg),with 6 rats in each group.Rats in the normal group and the model group were gavaged daily with sterilized water.Each group received daily interventions for 28 days.HE staining was used to observe pathological changes of gastric mucosa.Alisin Blue-Periodic Acid Schiff(ABPAS)stainingwas used to detect the intestinal metaplasia.The changes of gastric mucosal epithelial cells were observe by Scanning electron microscopy(SEM).The mRNA expressions of glucose transporter 1(Glutl),hexokinase 2(HK2),pyruvate kinase M2(PKM2),and lactate dehydrogenase A(LDHA)were detected using qRT-PCR.The protein expressions of Glutl,HK2,PKM2,LDHA,PI3K,AKT,and mTOR were detected using Western Blot.Results Compared with the blank group,the model group showed decreased body weight(P<0.01),reduced food intake,lethargy,and pathological changes in the gastric mucosa,including atrophy and intestinal metaplasia.mRNA and protein expressions of Glutl,HK2,PKM2,and LDHA increased(P<0.05,P<0.01),the protein expressions of PI3K,AKT,and mTOR increased in the model group(P<0.01).Compared with the model group,the body weight of rats in all intervention groups increased(P<0.01),and their food intake,body weight,and mental state were all improved;the Vitacoenzyme group and the CM low-dose group,as well as the CM high-dose group,all repaired the gastric mucosal damage in CAG model rats from a pathological perspective and alleviated intestinal metaplasia.Compared with the model group,the levels of Glutl,HK2,and PKM2 mRNA reduced in all intervention groups(P<0.01),and the level of LDHA mRNA decreased in the CM high-dose group(P<0.01).Additionally,the protein expressions of PKM2,LDHA,Glutl,HK2,PI3K,and mTOR reduced in the CM low-dose and high-dose groups(P<0.05,P<0.01),AKT protein expressions decreased in the CM high-dose group(P<0.01).Conclusion MLF may treat chronic atrophic gastritis by down-regulating key glycolytic targets(Glutl,HK2,PKM2,and LDHA)through inhibition of the PI3K/AKT/mTOR pathway.展开更多
文摘Objective To investigate the effect of modified Leweiyin Formula(MLF)on key glycolytic regulatory targets in the gastric mucosa of rats with chronic atrophic gastritis(CAG)based on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signalingpathway.Methods The CAG rat model was induced using a combination of free drinking of 1-methyl-3-nitro-1-nitrosoguanidine(MNNG),oral administration of sodium salicylate,and an irregular feeding schedule.After modeling,except for the blank group,the remaining rats were randomly divided into the model group,Vitacoenzyme group,Chinese medicine(CM)low-dose group(6.3 g/kg),and CM high-dose group(25.2 g/kg),with 6 rats in each group.Rats in the normal group and the model group were gavaged daily with sterilized water.Each group received daily interventions for 28 days.HE staining was used to observe pathological changes of gastric mucosa.Alisin Blue-Periodic Acid Schiff(ABPAS)stainingwas used to detect the intestinal metaplasia.The changes of gastric mucosal epithelial cells were observe by Scanning electron microscopy(SEM).The mRNA expressions of glucose transporter 1(Glutl),hexokinase 2(HK2),pyruvate kinase M2(PKM2),and lactate dehydrogenase A(LDHA)were detected using qRT-PCR.The protein expressions of Glutl,HK2,PKM2,LDHA,PI3K,AKT,and mTOR were detected using Western Blot.Results Compared with the blank group,the model group showed decreased body weight(P<0.01),reduced food intake,lethargy,and pathological changes in the gastric mucosa,including atrophy and intestinal metaplasia.mRNA and protein expressions of Glutl,HK2,PKM2,and LDHA increased(P<0.05,P<0.01),the protein expressions of PI3K,AKT,and mTOR increased in the model group(P<0.01).Compared with the model group,the body weight of rats in all intervention groups increased(P<0.01),and their food intake,body weight,and mental state were all improved;the Vitacoenzyme group and the CM low-dose group,as well as the CM high-dose group,all repaired the gastric mucosal damage in CAG model rats from a pathological perspective and alleviated intestinal metaplasia.Compared with the model group,the levels of Glutl,HK2,and PKM2 mRNA reduced in all intervention groups(P<0.01),and the level of LDHA mRNA decreased in the CM high-dose group(P<0.01).Additionally,the protein expressions of PKM2,LDHA,Glutl,HK2,PI3K,and mTOR reduced in the CM low-dose and high-dose groups(P<0.05,P<0.01),AKT protein expressions decreased in the CM high-dose group(P<0.01).Conclusion MLF may treat chronic atrophic gastritis by down-regulating key glycolytic targets(Glutl,HK2,PKM2,and LDHA)through inhibition of the PI3K/AKT/mTOR pathway.
