| Objective(1)Clinical trialsBy comparing the curative effect and quality of life of patients with chronic atrophic gastritis before and after treatment,the clinical efficacy of the method of tonifying spleen and clearing heat and invigorating blood circulation(using Compound Wei Wei Qing Granules)on CAG patients was determined.(2)Animal experimentTo study the effect of tonifying spleen and clearing heat and invigorating blood circulation on the treatment of atrophic gastritis by using Compound Wei Wei Qing Granules in rats with CAG.By observing the overall situation of rats with chronic atrophic gastritis,gastric mucosa pathological changes of gastric mucosa of TNF-alpha and IKK and P50 and other related indicators,we aims to investigate the relationship between gastric mucosal atrophy and carcinogenesis and inflammatory pathways,providing the theoretical basis for the effect mechanism of Chinese medicine.Methods(1)Clinical trialsAfter a multicenter study,a total of 78 patients were enrolled in the clinical trial,42 patients in the Wei Wei Qing group and 36 cases in the folic acid group.A total of 76 patients were involved in the data analysis,of which 2 patients were lost.4 patients in folic acid group refused the reexamination of gastroscopy,so it is not included in the pathological efficacy comparison.Before and after treatment,patients were evaluated for histopathological examination,endoscopic evaluation,and the scale of SSDPRO-CG.The outcome scale was used to assess the performance and quality of life in patients with chronic gastritis.(2)Animal experimentIn this study,94 healthy male SPF SD rats were randomly divided into blank control group and CAG model group after adaptive feeding for 1 week.There were blank control group(n=14)and CAG model group(n=80).The blank control group was given normal diet,drinking water,until the end of the experiment.The CAG model group was given MNNG liquid and the concentration was 180g/mL,and we aimed to replicate spleen deficiency model on the basis of the classical hunger(i.e.feeding for 1 days,and then fasted for 1 days,so the cycle)until the fourteenth weeks.After examination of gastric mucosa pathological tissue,results showed that the gastric mucosa of two rats was gastric glands atrophy with intestinal metaplasia which was successful model.Then the CAG model group was randomly divided into 5 groups: model group,Wei Wei Qing high dose group,middle dose group,low dose group and Folic acid group.14 rats were in model group,then Wei Wei Qing high dose group,middle dose group,low dose group and folic acid group were respectively 16,normal control group and model control group were given normal saline.We started gavage from the fifteenth weeks,and drug concentration(crude drug)of Wei Wei Qing high dose group,middle dose group,low dose group were 15.6g/kg,7.8g/kg,3.9g/kg.Folic acid group began gavage from the fifteenth weeks using folic acid by the concentration of 1.46mg/kg/d.The volume of intragastric administration was 10ml/kg,once per day for 10 weeks.During the experiment,the rats were weighed every 2 weeks to observe the change of body weight.Electron microscopy,Real-time PCR and Western blot were used to detect the pathological changes of gastric mucosa and the changes of TNF-alpha,IKK,p50 and other indicators of NF-kappa B in rats.Results(1)Clinical trialsThere was no significant difference between two groups of patients in age,gender,education and other baseline comparisons.It can be considered that the baseline was no different between two groups of patients,statistical analysis can be carried out before and after treatment.First of all,it was about the pathological classification and curative effect.Before entering the group,two groups of patients all had atrophy and chronic inflammation;about intestinal metaplasia,two groups were statistically tested by chi square test,P>0.05,and the difference was not statistically significant;about dysplasia,after chi square test,P>0.05,there was no significant difference in activity;because smaller values of some parameters using Fisher’s exact probability,two-sided P>0.05,the difference was not statistically significant.Therefore,before treatment,the baseline of the two groups was consistent and the pathological classification was comparable.The two groups were compared before and after pathological classification.The rates of Wei Wei Qing group and folic acid group for improving atrophic lesions after treatment were 65% and 62.50%,the two groups can effectively improve patients with gastric mucosal atrophy,after the chi square test,P>0.05,the difference was not statistically significant.In the aspect of intestinal metaplasia,the rate of improvement in the treatment group was 36.67% and 31.82%,respectively.The two groups had some improvement in the intestinal metaplasia of the gastric mucosa.In the aspect of dysplasia,the two groups had no change before and after treatment,suggesting that the treatment group and the control group had no significant effect on gastric mucosal dysplasia.In the aspect of chronic inflammation,the rate of improvement was 25% and 18.75% in the treatment group and the folic acid group,and the chronic inflammation in the gastric mucosa was improved in the Wei Wei Qing group.The two groups compared with each other,due to the smaller number of parameters,using the Fisher ’s exact probability method,bilateral test P>0.05,the difference was not statistically significant.In the aspect of activity,10 cases and 8 cases of the treatment group and the folic acid group were treated respectively.Comparing before and after treatment,the gastric mucosa activity in the Wei Wei Qing group and the folic acid group were not significantly improved.Therefore,that atrophy of Wei Wei Qing and folic acid can improve gastric mucosa,and had a certain effect on the intestinal metaplasia,but had no effect on dysplasia,chronic inflammation and activity of gastric mucosa.There was no significant difference in the quality of life scores between the two groups before the treatment.After the treatment of Wei Wei Qing group,the quality of life of patients is better than that of the patients after the treatment of folic acid group.The main improvement is reflected in the spirit of color and digestive function.After statistical analysis,the quality of life of the patients in the treatment group was statistically significant,which indicated that the quality of life in the patients with the treatment group was better than that before the treatment.In addition to the total score,the areas of improvement included physiological areas,areas of independence,and psychological domains.It is suggested that Wei Wei Qing had better curative effect on improving the mental status and digestive function of the patients.It was embodied in the sense of relief,tired spirit complexion improvement,digestive function improved(belching,epigastric fullness,epigastric pain and other symptoms,and improve).The patients of independence and psychological and social areas of improvement were not obvious.There was no significant difference in the total scores of QOL between the two groups before and after treatment,indicating that the quality of life in the folic acid group was not significantly improved.Comparing the physiological field of digestive function suggested that folic acid in improving the digestive function of patients had certain curative effect.There were no significant differences in the quality of life scores between the pre and post scale scales in all areas,and there was no statistical significance.(2)Animal experimentAccording to the pathological examination,histopathology showed atrophic gastritis model was made with complex method of drinking MNNG with hunger,and the model was successfully made in the fourteenth week,a total of 2 rats were killed.Then the rats were randomly divided into five groups including 14 rats in model group,and the rats of Wei Wei Qing high dose group,middle dose group,low dose group and folic acid group were 16 respectively.In general,the weight of rats in the model group was significantly lighter than that in the blank group,and there was significant difference between the two groups.The weight gain of the model group was significantly lower than that of the blank group,and there was significant difference between the two groups.About the pathological morphology,Wei Wei Qing could improve the pathological changes of gastric mucosa in CAG rats to a certain extent,delay the progression of atrophic gastritis with intestinal metaplasia or dysplasia.In terms of electron microscope,Wei Wei Qing could improve chronic atrophic gastritis rat gastric mucosa through the general situation,the ultrastructure of gastric mucosal epithelial principal cells and parietal cells,thus affecting the secretion of gastric acid and pepsin,play a therapeutic effect.In terms of protein expression,Wei Wei Qing group can decrease the expression of TNF-alpha,IKK.Wei Wei Qing high dose group can down regulate the expression of p50,so as to control the development of CAG.ConclusionClinical trials showed that Wei Wei Qing could improve gastric mucosal histopathology.Judging from the case analysis,it could improve the mucosal atrophy and intestinal metaplasia and so on.Compared with the western medicine group,the clinical symptoms and quality of life in Wei Wei Qing group can be improved obviously.The method of tonifying spleen and clearing heat and invigorating blood circulation representative of Wei Wei Qing can effectively improve the general condition of CAG rats,improve the histopathology and ultrastructure of gastric mucosa in rats,its mechanism may be in the way of inhibiting the NFB signal transduction pathway of proinflammatory cytokines,the low protein expression,thereby blocking the abnormal activation of the cell signal transduction pathway in order to achieve the purpose of preventing CAG.The method of tonifying spleen and clearing heat and invigorating blood circulation may inhibit the expression of tumor suppressor genes by inhibiting the abnormal activation of the signal pathway,and then activating the high expression of tumor suppressor genes.But the signal transduction pathway downstream target genes are numerous,but also accept the signal transduction pathway upstream,there was crosstalk between each other and the signaling pathway was not a one-to-one correspondence.Therefore,the specific mechanism of tonifying spleen and clearing heat and invigorating blood circulation method on CAG intervention remained to be further explored. |
