Theoretical Exploration,Mechanism And Clinical Effect Of Tongyang Sanjie Method In The Treatment Of Chronic Atrophic Gastritis

1 PurposeThe main cause of chronic atrophic gastritis is Helicobacter pylori,which is also influenced by diet,environment,immunity and medicine.At present,the disease can not be cured.There are many deficiencies in the treatment of symptom relief and prevention of precancerous lesions.According to the principle of individualization,it is the advantage of traditional Chinese medicine in the treatment of this disease to use drugs for different etiology and syndromes to relieve symptoms.From the perspective of traditional Chinese medicine,the causes of appeal reflect the characteristics of gastric Yang damage.Early research revealed that Xin’an medicine and Xin’an Wang’s internal medicine had unique ideas on pathogenesis,syndrome differentiation and medication of treating epigastralgia: Taking Tongyang Sanjie method as the treatment principle,and taking Gualou Xiebai Banxia decoction as the main component,aiming at the wide application of stomach Yang deficiency in the treatment of stomach diseases,they were also suitable for the clinical treatment of chronic atrophic gastritis.Based on the pathogenesis of chronic atrophic gastritis,combined with the previous research basis,this study explored the historical background and theoretical basis of the method of Tongyang powder and knot in the theoretical source,and explored the mechanism of gastric Yang deficiency in the pathogenesis of chronic atrophic gastritis.On the basis of this theory,the prescription of stomach Yang deficiency in Wang’s medical record of Xin’an was mined to find the rule of Tongyang Sanjie method.Further study on the mechanism of animal experiment and clinical effect of the formula.In the study of animal experimental mechanism,the intervention mechanism of this method on CAG inflammatory activity was verified by the expression level of NF-κB / COX-2 pathway,and its intervention mechanism on precancerous state of CAG was studied by hedgehog signaling pathway;in the observation of clinical effect,the improvement level of clinical symptoms,syndromes and quality of life of CAG was judged by comparing with the clinical study of Qizhi Weitong granules.To provide theoretical and experimental basis for further clinical and pharmacological research of this prescription.2 methodThe first part: to analyze the characteristics of prescriptions and drugs for gastric distention / stomachache in Wang’s internal medicine of Xin’anFrom the published "Wang Zhongqi medical case Xin’an medical records series" and "Wang Renzhi medical case" as well as the existing medical case manuscripts of Mr.Wang letao,we selected the ones that met the diagnostic standards of gastric distention and stomachache in traditional Chinese medicine,and the syndromes that met the characteristics of gastric Yang malaise,with a relatively complete history,tongue and pulse image and pathogenesis analysis,with a complete prescription,and medical cases of drug dosage included in the study.SPSS Clementine software was used for association analysis,and the third-order association was analyzed.The basic drug use and composition rules of Tongyang Sanjie method in Wang’s internal medicine of Xin’an were summarized for the second and third parts.The second part: Study on the mechanism of Tongyang Sanjie formula against chronic atrophic gastritis through NF-κB / COX-2 pathway and hedgehog pathway72 healthy Wistar rats were divided into blank group,model group,treatment group,control group,NF-κ B blocker group,hedgehog blocker group,12 rats in each group.In the treatment group,NF-κ B blocker group and hedgehog blocker group,Tongyang Sanjie group granule was used for 4 weeks,while in the control group,Wenweishu capsule powder was used for 4 weeks.The blank group and the model group were given the same amount of normal saline.Evp4593 0.2mg · 100g-1 and gdc-0449 0.2mg · 100g-1 were given to NF-κ B blocker group and hedgehog blocker group respectively for 4 weeks.N-methyl-N ’-nitro-N-nitrosoguanidine(MNNG)was used to simulate the animal model of chronic atrophic gastritis.The expression of NF-κ B and COX-2 in gastric tissue was detected by Western blot and RT-PCR respectively.In the same way,Western blot was used to detect the protein expression of Shh,PTCH and Gli-1.RT-PCR was used to detect the mRNA expression of Shh,PTCH and Gli-1 in gastric tissue,and to determine the level of hedgehog pathway.The third part:the clinical effect of Tongyang Sanjie formula on chronic gastritis of gastric Yang deficiency type60 patients with chronic atrophic gastritis were randomly divided into observation group and control group.There were five significant differences in the general situation of each group.Observation group: take 300 ml Tongyang Sanjie group granules twice in the morning and evening.The control group was given Wenweishu capsule,1.2g once,twice a day.Before administration,one week after administration and four weeks after administration,TCM symptoms and symptom scores of each group before and after administration were scored.Before administration and four weeks after administration,gastrointestinal disease symptom overlap and pro scale scores were compared to evaluate the therapeutic effect of Tongyang Sanjie formula on TCM symptoms / syndromes and quality of life of patients with chronic gastritis of gastric Yang deficiency type.3 ResultsThe first part: to analyze the characteristics of prescriptions and drugs for gastric distention / stomachache in Wang’s internal medicine of Xin’anThe data mining of 147 eligible medical case groups showed that: Pinellia ternate,Gualou,Fructus aurantii;Pinelliae ternate,Gualou,Xiebai;Fructus aurantii,Gualou,Xiebai had the strongest correlation,which was significantly different from other drug combinations.It is concluded that four drugs,i.e.Fructus aurantii,Fructus Trichosanthis,Xiebai and pinellia,are the main drugs of Tongyang Sanjie formula in Wang’s internal medicine;based on other core drugs and second-order association rules,Tongyang Sanjie formula is composed of pinellia,Fructus Gualou,Xiebai,Fructus aurantii,Rhizoma Corydalis,Melia toosendanii,wulingzhi,Gansu pine and Rhizoma Coptidis.According to the similarity of composition and efficacy of this recipe,it should be flavored by Gualou Xiebai Banxia decoction.The second part: Study on the mechanism of Tongyang Sanjie formula against chronic atrophic gastritis through NF-κB / COX-2 pathway and hedgehog pathway(1)HE staining observation,the blank group showed normal gastric mucosa;blank group,model group,control group,treatment group,NF-κ B blocker group,Hedgehog blocker group showed atrophy and intestinal,consistent with the performance of atrophic gastritis;except blank group and NF-κ B blocker group,other groups of rats have active inflammation in the lamina propria,the degree of model group is more important than other groups.(2)Compared with the blank group,the expression of NF-κ B,COX-2 protein and mRNA in the model group increased significantly(P < 0.01);compared with the model group,the expression of NF-κ B,COX-2 protein and mRNA in the treatment group,the control group and the NF-κ B blocker group decreased(P < 0.05).Compared with the control group,there was no significant difference in the expression of NF-κ B,COX-2 protein and mRNA(P > 0.05).Compared with NF-κ B blocker group,NF-κ B,COX-2 protein and mRNA in the treatment group were higher(P < 0.05).(3)Compared with the blank group,the expression of Shh,PTCH,Gli-1 protein and mRNA in the model group decreased significantly(P < 0.01).Compared with the model group,the expression of Shh,PTCH,Gli-1 protein and mRNA in the treatment group and the control group were significantly higher(P < 0.01);there was no significant difference in Hedgehog blocker group(P > 0.05).There was no significant difference in Shh,PTCH,Gli-1 protein and mRNA expression between the two groups(P > 0.05).Compared with the hedgehog group,Shh,PTCH,Gli-1 protein and mRNA expression in the treatment group increased(P < 0.01).The third part: the clinical effect of Tongyang Sanjie formula on chronic gastritis of gastric Yang deficiency type(1)Compared with the control group,the scores of TCM symptoms and syndromes in the treatment group and the observation group were significantly lower than those before administration(P < 0.05),and the scores of 4 weeks were significantly lower than that of 1 week after administration(P < 0.05).Compared with the control group,there was no significant difference in the main symptom score of the observation group before administration,one week after administration and four weeks after administration(P > 0.05);after four weeks of administration,the secondary symptom score and syndrome score of the observation group were significantly lower than that of the control group(P < 0.05).(2)After 4 weeks of administration,the scores of reflux,dyspepsia,abnormal defecation and general symptoms were lower than those before administration(P < 0.05);there was no significant difference in scores of psychological factors and social factors between the two groups(P > 0.05).There was no significant difference in the scores of reflux,dyspepsia,abnormal defecation,systemic symptoms,psychological factors and social factors between the observation group and the control group before treatment(P > 0.05);after 4 weeks of administration,the observation group was better than the control group in the scores of dyspepsia and reflux symptoms(P < 0.05);in the scores of abnormal defecation,systemic symptoms,psychological factors and social factors,the observation group was better than the control group(P < 0.05)There was no significant difference between the observation group and the control group(P > 0.05).4 Conclusion(1)Wang’s internal medicine Tongyang Sanjie method in Xin’an is aimed at the stomach ruffian and stomach ache caused by stomach Yang depression.It is composed of Pinellia ternate,Gualou,Xiebai,Fructus aurantii,Rhizoma Corydalis,Melia toosendanii,wulingzhi,Gansu pine and Coptis.It is made by adding flavor to Gualou Xiebai Pinellia decoction.(2)Tongyang Sanjie method(modified by Gualou Xiebai Banxia Decoction)can inhibit the inflammatory activity of chronic atrophic gastritis by inhibiting the expression of NF-κ B,COX-2 protein and mRNA.(3)Tongyang Sanjie method(modified by Gualou Xiebai Banxia Decoction)can improve the expression of Shh,PTCH,Gli-1 protein and mRNA,activate hedgehog pathway,inhibit the precancerous state of chronic atrophic gastritis and the transformation to gastric cancer.(4)Tongyang Sanjie method(modified by Gualou Xiebai Banxia Decoction)is superior to Yangweishu capsule in relieving the clinical symptoms and syndromes of patients with chronic atrophic gastritis,dyspepsia and reflux symptoms.