| BackgroundChronic atrophic gastritis is a type of chronic gastritis,refers to the gastric mucosa inherent gland atrophy,may be associated with intestinal metaplasia and dysplasia,bringing serious public health and social problems,seriously affect the social capacity of patients and Quality of life.Chronic atrophic gastritis is a link between chronic superficial gastritis and stomach cancer,is the key stage of gastric mucosa malignant transformation,based on in-depth study of mechanism of chronic atrophic gastritis,can not only to reveal the pathogenesis of inflammation leading to inflammatory tumorsat a certain extent,but also can implement more targeted prevention measures,reduce the incidence of gastric cancer and mortality.Weiweiqing is the empirical prescriptionof the treatment of chronic atrophic gastritis in our clinic,which parts ofastragali,atractylodes,Scutellaria barbata,rhizoma zedoariae,Radix Fici Hirtae and Fructus aurantii,altogether playsInvigorating spleen,regulating qi,dissipate blood stasis and detoxify,in order to promote the recovery of viscera function,improve the patient's clinical symptoms first.JAK2/STAT3 signaling pathway is closely related to the inflammatory response.Activated STAT3 can induce the expression of Bcl-2 and Bcl-xL genes,which inhibit the apoptosis of gastric mucosa cells,promote the gastric mucosa chronic inflammation related gastric cancer occurs,thus inhibiting JAK2/STAT3 signaling pathway provides a possibility of prevention and treatment of gastric cancer.The purpose of this study was to assess the clinical efficacy and safety of Weiweiqing granule in the treatment of chronic atrophic gastritis,and take the JAK2/STAT3 pathway as a starting point,analysis the mechanism of Weiweiqing on chronic atrophic gastritis(CAG)rats,to further reveal the molecular mechanism of Weiweiqing to improve the pathology of chronic atrophic gastritis.Objective(1)To evaluate the clinical efficacy and safety of Weiweiqing granule in the treatment of chronic atrophic gastritis.(2)In this study,weuse MNNG cooperate hunger disorder to establish the rat model of chronic atrophic gastritis,and to observe the effect of Weiweiqing Granule on the general situation of chronic atrophic gastritis..At the same time discusses the curative effect of Weiweiqing on atrophy and intestinal metaplasia.(3)To investigate the role of JAK2/STAT3 in the pathogenesis of chronic atrophic gastritis by observing the expression of JAK2/STAT3 signaling pathway in chronic atrophic gastritis.Methods(1)Clinical study:Patients with chronic atrophic gastritis who were included in the spleen and stomach weak were randomly divided intotwo groups:Weiweiqinggroup and folic acid group.Weiweiqinggroup was treated with Weiweiqing granules,1 bag 1 time,3 times per day.Folic acid group was given folic acid tablets,5mg 1time,3 times a day.After taking medicine of 24 weeks,the endoscopy was reviewed to assess changes in gastric mucosal atrophy,intestinal metaplasia,dysplasia,chronic inflammation,and inflammatory activity.And comparison between each group to observe the Weiweiqing and folic acid to improve the abdomen(diagnosis),epigastric pain(diagnosis)bilges frowsty,upper abdomen(diagnosis)blocking nausea,heartburn,acid reflux,belching,loss of appetite,eat less symptom integral,symptom total points.(2)Experimental study:94 SPF grade SD male rats aged 70-80 days and weighing 170-200g were randomly divided into two groups:blank group and chronic atrophic gastritis model group.14 rats in the blank group and 80 rats in the chronic atrophic gastritis model group.Blank group given a normal diet,free water.Chronic atrophic gastritis model group was given 180 ?g/mL MNNG drinking solution for free drinking,combined with the hunger aberration method 14 weeks to make chronic atrophic gastritis rat model,randomly selected two chronic atrophic gastritis model group mice.The pathology of gastric mucosal examination showboth ratsfound gastric mucosal atrophy with intestinal metaplasia,indicating successful modeling.After the success of the model of chronic atrophic gastritis,model group were randomly divided into 5 groups:model group,high dose group of Weiweiqing,middle dose group of Weiweiqing,low dose group of Weiweiqing,the folic acid group.Blank group and model group were given saline lavage.Carnitine concentration of high dose group of Weiweiqing,middle dose group of Weiweiqing,low dose group of Weiweiqing were 15.6 g/kg/d,7.8 g/kg/d,3.9 g/kg/d.Carnitine concentration offolic acid group was 1.46 mg/kg/d.Intragastric volume 10ml/kg,1 times per day,continuous gavage for 10 weeks.After the experiment took little stomach body side-sinus junction gastric mucosa,to prepare gastric mucosa epithelial tissue slice.HE staining to observe each rat gastric mucosa epithelial atrophy,intestinal metaplasia.AB-PAS staining to observe each rat gastric mucosa epithelium of intestinal metaplasia lesions scope;Scrape the remaining rat gastric mucosa,Western-Blot method to detect the expression of JAK2 and STAT3,p-STAT3.RT-PCR method to detect the expression of Bcl-2 and Bcl-xL.Result(1)Clinical study:The trial group included 64 cases,the treatment group of 34 cases,30 cases of control.Two patients with gastric dampness were dislocated,and a total of 62 patients were involved in data analysis.(1)Inpathological,Weiweiqing improved chronic inflammatory score better than folic acid group.(2)In the improvement of the main symptom points,the treatment group could improved upper abdominal(epigastric)pain better than the control group,the control group could improved upper abdominal(epigastric)fullness better than the treatment group,other aspects of the main symptom points,the difference was not statistically significant.(2)Experimental study:?HE staining showed that most of the gastric mucosa glands disappeared in the model group,the mucosal musclethickening,inflammatory cell infiltrating in the interstitial,lymphoid follicle formation,intestinal metaplasia can be found.There are varying degrees of degeneration or necrosis of the shedding cells,mucosal thinning,glandular cells arranged disorder,gland was cystic dilatation,epithelial cell morphology of different sizes,interstitial edema,congestion.Gastric mucosa showed full-thickness intestinal metaplasia,showing a large number of goblet cells.The gastric mucosa of folic acid group was pink,poor gloss,thinning,folds disorder,and a large number of inflammatory cell infiltration was seen.And interstitial edema,congestion,inflammatory cell infiltration was seen,regional mucosa can be seen a large number of intestinal metaplasia.The pathologic changes of the three dose groups were between the folic acid and the blank group,the pathological changes of the high dose group were the most obvious,middle dose group followed,and the effect of the low dose group was not obvious.AB-PAS staining showed no blue or purple intestinal metaplasia lesions in the blank group;Diffuse intestinal metaplasia appeared in the model group,after treatment with Weiweiqing group,mainly concentrated in the stomach cavity side of the cell,the high dose of Weiweiqing group and middle dose of Weiweiqing group improved most obviously,folic acid group show no obvious improvement;? The expression of JAK2 protein in the model group was the highest,and the expression of JAK2 protein in the high dose group of Weiweiqing was lower than that in the model group.The expression of STAT3 protein in the model group was the highest,and the expression of STAT3 protein in the three dose of groups of Weiweiqing was lower than that in the model group.The high dose group was the most obvious.The expression of p-STAT3 protein in the model group was the highest,and the expression of p-STAT3 protein in the three groups of Weiweiqing was lower than that in the model group,and the high dose group was significantly lower than that of the model group.Compared with the model group,the expression of Bcl-2 mRNA in the high dose group of Weiweiqing was significantly lower than that in the model group(P<0.05).Compared with the model group,the expression of Bcl-xL mRNA in the high dose group was significantly lower than that in the model group(P<0.05).Conclusion(1)Weiweiqing can improve the pathology of chronic inflammatory score.At the same time,Weiweiqing can improve the upper abdomen(epigastric)pain.This provides clinical evidence for the treatment of chronic atrophic gastritis.(2)In this study,the model of chronic atrophic gastritis was successfully reconstructed by the comprehensive modeling method of MNNG solution free drinking and hunger and deprivation.(3)Weiweiqing could ease atrophy and intestinal metaplasia to a certain extent.(4)Activation of JAK2/STAT3 in chronic atrophic gastritis stage may be an important step to promote mucosal cell hyperplasia and participate in the process of malignant transformation of gastric mucosa.Weiweiqing could inhibit the activation of JAK2/STAT3 signaling pathway to a certain extent. |
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