Study On The Efficacy And Mechanism Of Banxia Tiaozhong Granules On Non-erosion Reflux Disease Based On The "Coordination Theory Of Spleen Ascending And Stomach Descending"

This paper discusses the cognition of non-erosive reflux disease(NERD)in traditional Chinese medicine(TCM)through following parts including literature,clinical and animal experimental study.1.Theoretical Origin and Research Progress of "the Coordination Theory of Spleen Ascending and Stomach and Descending" in the treatment of non-erosive reflux disease:The “coordination theory” was first recorded in Neijing,which laid its theoretical foundation.In the Eastern Han Dynasty,Zhang Zhongjing fully applied the theory in Neijing to the cure of spleen and stomach diseases,which promoted the formation and development of "the coordination theory".Li Dongyuan further promoted the development of the theory.Since then,the physicians of successive dynasties have enriched and improved the theory.In addition,modern doctors are also continuously inherit and innovate the theory.Our famous professor Zhang Jiemei,who has plenty of experience in treating NERD,applies "the coordination theory" to the clinical practice,and holds that the disorder of spleen and stomach function is the key pathogenesis of NERD.Therefore,to restore the "spleen ascending and stomach descending function" is the core and fundamental.Based on it,he created Banxia Tiaozhong Granules in treating NERD,which shows a remarkable curative effect.Therefore,Banxia Tiaozhong Granule has sufficient theoretical basis and research value in the treatment of NERD based on the "coordination theory".2.Analysis of Prescription Medication Rule of TCM Treatment of NERD based on Data Mining:Objective: To explore the medication rule of TCM in the treatment of NERD through the method of data mining and "Ancient and contemporary medical case report cloud platform" system.Methods: Search the effective prescription of TCM in treating NERD in recent 10 years though Chinese databases such as Wanfang,VIP and Zhiwang,in order to set a database of NERD prescription.Explore the medication rule of TCM in the treatment of NERD by Analyzing the drug attributes,associations and frequency statistics,building a Chinese herb complex network through the platform above.Results: A total of 418 articles were acquired,in which 351 were excluded after selecting,and 67 were finally included,involving 83 prescriptions,121 Chinese medicines and 4 main syndrome types.The data of drug frequency,associations and drug core network were analyzed and summarized,and the rule of prescription was further summarized.Conclusion: TCM treatment of the disease with pinellia,radix glycyrrhizae,radix bupleuri,rhizoma coptidis medicine as the core drugs,with sheen open bitter drop,liver spleen and stomach drop counter drug as the main characteristics.And the general and fundamental therapeutic principle is the adjustment of the coordination of spleen and stomach function,taking into account various treatments such as dissipating cold and clearing heat,regulating qi and reducing phlegm.These results provide a model for clinical treatment and subsequent research of NERD.3.Study on Clinical Efficacy of Banxia Tiaozhong Granule in Treating NERD of Cold and Heat Mixed Type:Objective: To observe the clinical efficacy of Banxia Tiaozhong Granule in the treatment NERD of cold and heat mixed type.Methods: A total of 84 patients with cold and heat mixed type of NERD were randomly divided into experimental group and control group,with 42 cases in each group,from August 2020 to October 2021.Experimental group was given Banxia Tiaozhong Granule 1 pack/ time,3 times/day,and pantoprazole 40 mg,once a day;The control group was offered pantoprazole only 40 mg,once a day,and the course of treatment was 4 weeks.After treatment,the basic conditions and the safety of both groups were evaluated,and the scores of reflux symptom VAS,TCM syndrome,PRO scale,SAS/SDS scale,Gerd Q,GERD-HRQL were compared between both groups,and the curing effect of TCM syndrome was evaluated.Results: Intra-group comparison showed that,compared with prior treatment,the score,TCM syndrome,GERD-HRQL scale,PRO scale and SAS/SDS scale score were decreased after treatment in both groups(P < 0.01).Comparison between groups showed that VAS and TCM syndromes score in the experimental group were lower than those in the control group(P < 0.01),especially in retrosternal burning or epigastric burning discomfort,acid reflux or water vomiting,fatigue,bowel rumble and stool,and hand and foot temperature(P < 0.01).The total effective rate of experimental group(95.24%)was higher than that of control group(78.57%)(P < 0.05).Meanwhile,compared with the control group,the scores of GERD-HRQL,PRO and SAS/SDS scale in the experimental group were lower(P < 0.01).Conclusion: Banxia Tiaozhong Granule combined with PPI can relieve the relevant clinical symptoms and TCM syndromes of NERD,and the efficacy is significantly better than PPI alone.Besides,it can also improve the life quality and psychomental state of NERD patients,without obvious adverse reactions,showing its good safety and curing effects.4.Study on the Mechanism of Banxia Tiaozhong granule in Treating NERD based on MC-PAR-2-CGRP pathway:Objective: To investigate the mechanism of Banxia Tiaozhong Granule in the treatment of NERD by observing the behavioral and histological changes of pain sensation and the expression of visceral hypersensitivity factors in NERD model rats.Methods: 48 male SD rats were put to 6 groups randomly.Control group and model group were administrated saline intervention;while Banxia Tiaozhong granule group,omeprazole group and PAR-2 antagonist group were administrated corresponding drug intervention respectively.Banxia Tiaozhong granule+PAR-2 agonist group were treated with Banxia Tiaozhong granule and PAR-2 agonist simultaneously.After 14 days,general condition,mechanical foot contraction reflex threshold,morphological changes of esophageal tissue,mast cell count,and the expression of related factors were examined by RT-PCR and Western Blot in esophageal tissue.Results: Compared with control group,MWT of model group was decreased(P < 0.05),microinflammatory changes were observed in esophageal tissue,MC count was raised(P < 0.05),and protein and m RNA expressions of SP,CGRP,TRPV1 and PAR-2 were climbed(P < 0.05).Compared with model group,MWT of PAR-2antagonist group,Banxia Tiaozhong Granule group and omeprazole group were declined(P < 0.05),MC count and the expression of above related factors were both declined(P <0.05).It showed no difference between Banxia Tiaozhong granule+PAR-2 agonist group and model group(P > 0.05).Conclusion: Banxia Tiaozhong granules can down-regulate the expression levels of CGRP,SP and other neurotransmitters by mediating mast cell-PAR-2-CGRP pathway,and relieve the hypersensitivity of esophagus and viscera in rats of NERD model,which may be one of its therapeutic mechanisms for NERD.