| Objective:To study the effect of Xin Gastric granule on signal pathway Pi3k/akt and the regulation of P-GP granule on its downstream P-GP expression on the control platform of Pi3k/akt signaling pathway,to reveal the preventive effect and mechanism of Xin Gastric granule on gastric precancerous lesion,It provides a theoretical basis for the prevention and treatment of gastric precancerous lesion and its role in reversing multidrug resistance of gastric cancer.Methods:210 Healthy male Wistar rats were numbered according to their weight,the Wistar rats were randomly divided into 7 groups,namely the normal control group(N,N=30),the Model control group(M,N=30),the control group(W,N=30),the control group(V,N=30),Xin Gastric granule high dose Group(hx,n=30),Xin Gastric granule dose Group(mx,n=30),Xin Gastric granule low Dose Group(lx,n=30).Free-use n-methyl-n’-nitro-N-Nitro-Guanidine(MNNG),using standard feed ranitidine feeding,hot saline filling stomach,and combined with hunger Disorder compound modeling method.While the rats were modeled,the drug groups were given corresponding control drugs to intervene.HX,MX,LX Group:respectively,the 8.60g/kg,4.30 g/kg,2.15g/kg stomach powder,1 times a day.V Group:0.32g/kg,gastric lavage,1 times a day.W Group:Gastric spring 0.39g/kg,irrigation stomach for medicine,1 times a day.N,M Group:Give the same volume of distilled water,irrigation stomach for medicine,1 times a day.To the end of 16w randomly selected m group of rats were examined for pathological histology of gastric mucosa,and the model was confirmed to be completely discontinued and the intervention drugs were completed after 4.After successful preparation of the model,all rats were executed,the stomach was taken by laparotomy,and the gastric mucosa was observed by the naked eye and light microscope,and the akt,nf-κb,cox-2 of gastric mucosa was detected by immunohistochemical method,real time PCR and Western blot method.Expression of P-GP gene and protein.Results:(1)The general situation of rats:the macroscopic characterization(fur color,reaction sensitivity,stool)and weight gain of M group were significantly worse than N group.Compared with M group,the macroscopic representation and weight gain of rats were significantly improved,the difference was statistically significant(p<0.05,p<0.01),and the MX group was the most obvious improvement in each drug delivery group(p<0.05,p<0.01).(2)Pathological histology of gastric mucosa showed that the incidence of PLGC in M group was significantly higher than that in N Group(p<0.01),the incidence of PLGC in rats was significantly decreased compared with M group,and the difference was statistically significant(p<0.01).There was no significant difference in the incidence of PLGC between the drug delivery groups(p>0.05).(3)The results of Immunohistochemistry showed that the expression of Akt,NF-κb,COX-2 and P-GP protein in M group increased significantly compared with N group,and the difference was statistically significant(p<0.05).Compared with M group,each drug delivery group AKT,NF-κb,COX-2,The expression levels of P-GP protein were significantly decreased,especially in MX and HX Group,and there was no significant difference between the two groups(p>0.05).(4)The results of RT-PCR showed that the transcription levels of M group Akt,NF-κb,COX-2 and P-gpmrna increased significantly compared with N group,and the difference was statistically significant(p<0.05),and compared with M group,each drug delivery group AKT,NF-κb,COX-2,P-gpmrna transcription levels were significantly reduced,the difference was statistically significant(p<0.05),and in each drug group,especially in the MX group AKT,NF-κb,COX-2,P-gpmrna transcription levels were most obvious,P-gpmrna transcription level MX,HX group decreased most obviously,But there was no significant difference(p>0.05)between the two groups,and the difference was statistically significant(p<0.05).(5)Western blot results showed that:compared with n Group,the expression level of Akt,NF-κb,COX-2 and p-gp eggs in M group increased obviously,and the difference was statistically significant(p<0.05).Compared with M group,each drug delivery group AKT,NF-κb,COX-2,The expression of P-GP protein decreased significantly,especially in MX group,AKT,NF-κb,COX-2 and P-GP protein,the difference was statistically significant(p<0.05).Conclusion:(1)Xin Gastric granules can effectively improve the general state and macroscopic characterization of PLGC rat model,partially reverse pathological state of gastric mucosa in rats and reduce the incidence of PLGC.(2)The expression of Akt,NF-κb,COX-2 gene and protein in gastric tissue of PLGC rat model can be improved by reducing the apoptosis of gastric mucosal epithelial cells and cell proliferation.(3)The expression of P-GP gene and protein in gastric tissue of PLGC rat model can be lowered by Xin Gastric granule.(4)Xin-Gastric granules can further mediate the low expression of P-GP by inhibiting the activation of pi3k/akt signaling pathway. |
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