Mechanism Research Of Weiqi Decoction Attenuated Chronic Atrophic Gastritis Based On COX-2/HIF-1?/VEGF Pathway

Objective:The purpose of the study was to determine the best modeling time of inducing chronic atrophic gastritis(CAG)in rats by saturated NaCl and MNNG,and investigate the dynamic changes of gastric mucosal blood microcirculation and the gene and protein expressions of the COX-2/HIF-1?/VEGF signaling pathway during the development of chronic atrophic gastritis,so as to research the possible mechanism of "qi deficiency and blood stasis" on CAG.Also,to clarify the effect and molecular mechanism of Weiqi Decoction with the effect of "tonifiying qi and smoothing the blood" attenuated CAG rats,based on the changes of gastric mucosal blood microcirculation and COX-2/HIF-1?/VEGF signaling pathway.Method:1.Forty-five male Wistar rats were assigned randomly into two groups:normal control group(n=10)and model group(n=35).MNNG and saturated NaCl were used to induce CAG in rats by intragastric gavage.Every 5 model rats was sacrificed every 5 weeks,at the end of every weeks,started from the 5th week to the 35th week.Gastric mucosal blood flow(GMBF)was measured by Laser Doppler Flowmetry.The pathological changes of the gastric mucosa were detected by HE staining and AB-PAS staining.Gene expressions of COX-2,HIF-1?,VEGF,VEGFR1 was detected using Quantitative PCR method.Protein expressions of COX-2,HIF-1?,VEGFR1 in the gastric tissues were assayed by using western blotting approach.2.Forty-eight male Wistar rats were divided randomly into six groups:control group,model group,Folic acid group,WQD-treated groups at doses of 4 g/kg,2 g/kg,1 g/kg,with eight rats in each group.MNNG and Saturated NaCl was used to induce CAG rat with precancerous lesion(intestinal metaplasia and dysplasia).At the same time,treatments of Weiqi decoction and folic acid was given for 25 weeks,started from the 15th week.After the modeling and treatments,gastric mucosal blood flow was measured using Laser Doppler Flowmetry.The pathological changes of the gastric mucosa were identified by HE staining and AB-PAS staining.The protein expression of COX-2,HIF-1?,VEGFR1 in the gastric tissues were measured by western blotting approach.Gene expression of COX-2,HIF-1?,VEGF,VEGFRlwas detected by using Quantitative PCR method.Result:1.MNNG and saturated NaCl was used to establish the CAG rat models and the GMBF was decreased as early as 15 weeks after modeling,but there was no pathology changes of atrophic gastritis.At the modeling time of 25 weeks,the protein expression of COX-2,HIF-1? were up-regulated and mild atrophy could be detected by pathologaicl stainings in model rats.Also,the mRNA expression of COX-2,HIF-1?,VEGF and VEGFR1 was enhanced as early as 25 weeks after model induction.And after 35-weeks modeling,moderate even severe pathological changes of atrophy and dysplasia appeared.Then the protein expressions of HIF-1?,COX-2 and VEGFR1 as well as the gene expressions of COX-2,HIF-1?,VEGF and VEGFR1 were totally increased at 35th week after model induction.2.After treatment of WQD,compared with control rats,the microcirculation disturbance of gastric mucosa as well as atrophy and intestinal metaplasia were induced in the stomach of CAG rats identified by microcirculation measurement as well as the HE and AB-PAS staining,which could be significantly attenuated by WQD treatment and folic acid treatment.Moreover,the protein expression of COX-2,HIF-1? and VEGFR1 in gastric tissues of pylorus was obviously increased.Also,the gene expression of HIF-1??COX-2?VEGF?VEGFR1 was up-regulated.Conclusion:MNNG and saturated NaCl by gavage for 35 weeks could successfully induce CAG in rats.Moreover,the microcirculation disturbance of gastric mucosa and abnormal activation of COX-2/HIF-1?/VEGF signaling pathway may have the relationship with the pathogenesis of "qi deficiency and blood stasis".And,WQD can attenuated CAG through improving the microcirculation disturbance of gastric mucosa and regulating COX-2/HIF-1?/VEGF signaling pathway.