Study On The Mechanism Of Maxing Ganshi Decoction In Treating Asthma And The Significance Of The Compatibility Of Monarch, Minister And Adjuvant

BackgroundAsthma is a common chronic respiratory disease that seriously endanger human health.At present,Western medicine has certain limitations.Traditional Chinese medicine(TCM)has the advantages of few side effects.Therefore,from the perspective of TCM to find a way to treat asthma,combining TCM and Western medicine to treat asthma is a current medical development direction.Ma Xing Gan Shi Decoction(MXGSD)is the main prescription of"Shang Han Lun".The National Key Basic Research and Development Program,which is responsible by Professor Fu Yanling and Professor Xiao Lin,has found that MXGSD is effective in the treatment of pneumonia.And,many doctors mainly apply MXGSD in the treatment of pneumonia,but there is still no scientific basis for the therapeutic effect,mechanism of action and the compatibility of Junchen Zuoshi in the treatment of asthma.Therefore,this topic apply the methods of systematic evaluation,network pharmacology,and animal experiments to study the efficacy,mechanism of action and the significance of the compatibility of Junchen Zuoshi in MXGSD treating asthma,in order to contribute to the clinicalObjective1.To systematically evaluate the effectiveness and compatibility of the treatment of asthmatic disease with MXGSD,and analyze the clinical phenotype of asthma in which MXGSD is mainly used for treatment,and to explore its clinical compatibility and dosage2.Through the research on the pharmacology of asthmatic diseases in the treatment of asthmatic diseases,the main mechanism of action was predicted from the perspective of the overall system,and the main signaling pathways embodying the compatibility of Junchen Zuoshi3.Combining the results of 1 and 2,observe the clinical doses of MXGSD and its different Junchenzuoshi combined with decomposed formulas on the general state,body weight,asthmatic latency,behavioral evaluation,EOS count,IgE level,asthmatic rats,IL-4 level,IFN-? level,HE staining,and the intervention of the main signaling pathways of Junchenzuoshi's compatibility significance,preliminary explanation of the mechanism of action of MXGSD in the treatment of asthma and the compatibility of Junchen ZuoshiMethod1.A literature review of 10 randomized controlled trials of MXGSD in the treatment of asthmatic diseases.The subjects included in the study were asthma patients.The intervention was oral MXGSD(increased medicinal taste ?5),and the control measures were no treatment,placebo,or western medicine.Outcome measures included effective and biochemical indicators.Such as the main outcome indicators,and the improvement of clinical symptoms and signs,asthma control,adverse reaction rate and other secondary outcome indicators.Literature screening and exclusion,data extraction and literature quality risk assessment were performed according to the Cochrane systematic review manual.Data analysis,data synthesis and publication bias were performed using Stata 15 software2.Literature search 10 databases,collect as much as possible the chemical composition and pharmacokinetics information of MXGSD,screen the effective chemical components,and target gene.At the same time,the literature retrieved five disease target gene databases and collected target genes for asthma diseases.Cytoscape 3.2.1software was used to construct the MXGSD-asthma disease-target gene network,and the core target of MXGSD in the treatment of asthmatic diseases was screened,and clustering and enrichment analysis were carried out to predict the main mechanism of action.At the same time,the differences of KEGG signaling pathways in different asthmatic diseases involving the different herbs of MXGSD were carried out,and the main signal pathways reflecting the compatibility of the compound Junchen Zuoshi were predicted.3.Establish a rat model of OVA-sensitized asthma,and divide it into 7 groups,namely blank control group,asthma model group,Mahuang group,Ma Xing group,Ma Cao group,Ma Xingcao group,and MXGSD group,each group12,drug intervention for 10 days,observe the general state,body weight,asthma latency,behavioral evaluation,EOS count,IgE level,IL-4 level,IFN-y level,HE staining,and the significance of the compatibility of Junchen Zuoshi.The changes of signal pathway indicators were discussed to explore the intervention effect of MXGSD and its different compatibility prescriptions on asthma.Result1.Systematic review results:The study finally included 19 randomized controlled trials involving a total of 1407 patients,more adults than children,more men than women,of which the disease phenotype is the most common bronchial asthma,TCM syndrome type with lung The heat syndrome is more common.The commonly used dosage of MXGSD is Mahuang 6g,Xingren 9g,Gancao 6g,Shigao 30g.The commonly used drugs in clinical practice are huangqin,beimu,chantui,jiegeng,sangbaipi,jiangcan,dilong,pipaye,gualou,suzi,banxia,shegan,the number of daily service is 2 times.Document quality risk assessment is vague.13 cases were treated with MXGSD+Western medicine VS Western medicine for bronchial asthma,3cases were treated with MXGSD VS Western medicine for bronchial asthma,and 1 case was MXGSD+Western medicine VS Western medicine for cough mutation In the study of asthma,2cases were treated with MXGSD VS Western medicine for cough variant asthma.Because some outcomes reported that the number of trials was too small or the clinical heterogeneity was too large,no meta-analysis was performed.Among them,MXGSD+Western medicine compared with western medicine in the treatment of adult bronchial asthma in total effective rate(RR:1.214,95%Cl:[1.08,1.36]),clinical control rate(RR:1.904,95%Cl:[1.46],2.47]),FEV1(MD:0.394,95%Cl:[0.20,0.58]),FEV1%(MD:14.234,95%Cl:[10.30,18.16]),PEF(MD:1.694,95%Cl:[0.89,2.50]),EOS(MD:-0.034,95%Cl:[-0.05,-0.01]),ACT score(MD:0.984,95%Cl:[0.29,1.67]),acute after 12 months of treatment The number of episodes(RR:0.604,95%Cl:[0.43,0.82])was statistically significant.The main effective rate(RR:1.264,95%Cl:[1.10,1.45])and the clinical control rate(RR:1.424,95%Cl:[1.06,1.89]),wheezing score(MD:-0.894,95%Cl:[-1.24,-0.54]),cough score(MD:-0.324,95%Cl:[-0.47,-0.17]),cough score(MD:-0.114,95%Cl:[-0.18,-0.04]),snoring score(MD:-0.134,95%Cl:[-0.23,-0.03]),wheezing score(MD:-0.44,95%Cl:[-0.18,-0.02])was statistically significant;there was no statistically significant difference in the incidence of adverse events(RD:0.00495%Cl:[-0.04,0.04])..The effect of MXGSD on the total effective rate of bronchial asthma in children(RR:1.224,95%Cl:[1.06,1.41])and clinical control rate(RR:1.744,95%Cl:[1.17,2.58])is statistically significant.Using the Stata 15 software to conduct a publication bias test on the total effective rate and clinical control rate(inclusion of? items)of "MXGSD+Western Medicine VS Western Medicine for Bronchial Asthma",there was a publication bias,but The effect of publication bias on the results of the study was analyzed by shearing method.The results showed no statistical significance,indicating that the results were stable and relatively reliable2.Network pharmacology research results:Through database search,a total of 600 chemical components related to MXGSD were collected,corresponding to 141 target genes.Collect 542 target genes related to asthma diseases.The PPI data network of "MXGSD-Asthma Disease-Target Gene"was established,and a total of 138 core targets were screened for core target topology.GO annotation of 138 core targets revealed that it mainly focused on ?gene expression,silencing and replication,?DNA/RNA damage repair and transcriptional regulation,?protein classification,modification,synthesis and stabilization,?signal transduction of inflammatory immune responses,and cascade activation,?DNA/RNA regulation;and TOP3 signaling pathway in KEGG signaling pathway enrichment analysis is neurotrophic factor,estrogen,and PI3K-Akt signaling pathway.At the same time,differential analysis of the different KEGG signaling pathways involved in the asthmatic disease was carried out on the different traditional Chinese medicines of MXGSD.It is speculated that the PI3K-Akt signaling pathway,estrogen signaling pathway,and platelet activation may reflect the compatibility of Junchen Zuoshi.3.Animal experimental results:?General status:There was no obvious asthma in the rats in the blank control group,and the rats in asthma model group,Mahuang group,Ma Xing group,Macao group,Ma Xingcao group and MXGSD group had different asthma performance.?Body weight changes:The body weight of each group showed an increasing trend,but the difference in growth was not obvious,and there was no statistical significance.?Determination of the incubation period of asthma:The different compatibility of MXGSD can shorten the asthmatic time of asthmatic rats,and compared with asthma model group,there are statistical differences;the more the compatibility of the drug,the more obvious the statistical difference.?Behavioral evaluation:Different combinations of MXGSD can alleviate asthmatic symptoms such as cough,wheezing and snoring in asthmatic rats.Except for the Mahuang group,the other disassembled group has statistical significance compared with the asthma model group.But only MXGSD group and the Ma Xingcao group were statistically different from other compatible decomposed groups.? eosinophil count:different combinations of MXGSD can reduce the EOS level of asthmatic rats,but only the MXGSD and Ma Xingcao groups have statistical differences compared with asthma model group;And only MXGSD group was statistically different from Mahuang group and Maxing group.?IgE level:Different combinations of MXGSD can reduce the level of IgE in asthmatic rats,but only MXGSD group has statistical difference compared with asthma model group.?IL-4 level:Different combinations of MXGSD can reduce the level of IL-4 in asthmatic rats,and there are statistical differences.The more the compatibility of the drug,the more statistical difference.?IFN-? level:Different combinations of MXGSD can increase the level of IFN-? in asthmatic rats,but only MXGSD decoction group has statistical difference compared with asthma model group;The MXGSD group had statistical difference compared with asthma model group,Mahuang group,Maxing group and Macao group.?HE staining:There was no significant change in the blank control group under the microscope.A few of the bronchiole epithelium showed a small amount of shedding in the lung.The lymphocytes and a few granulocytes infiltrated around the connective tissue around the bronchiole,and the alveolar space was slightly thickened.But they are all mild.In other asthma model group,Mahuang group,Maxing group,Macao group,Ma Xingcao group and MXGSD group,the bronchiole epithelial cells were arranged disorderly and detached,mucus secreted in the airway,and connective tissue around the bronchioles.It can be seen that lymphocytes and most neutrophil infiltration,alveolar septal thickening and other typical asthma pathological manifestations,pathological damage severity.Pathological scoring criteria for lung injury showed that different combinations of MXGSD can improve inflammatory cell infiltration,bronchial epithelial cell shedding,alveolar septal thickening,etc.,but different combinations of disintegration Statistical differences were different,and the statistical difference was significant between the whole party and other different compatibility splits.?The expression of PI3K mRNA:The different compatibility of MXGSD can reduce the expression of PI3K mRNA in asthmatic rats,but only MXGSD group and Ma Xingcao group have statistical differences compared with asthma model group.Only MXGSD group was statistically different from the mahuang group and the macao group.11The expression of AKT mRNA:The different compatibility of MXGSD can reduce the expression of AKT mRNA in asthmatic rats.The other combinations of the dissociation group except the ephedra group have statistical difference compared with asthma model group.But there was no statistical difference between the two groups.Conclusion1.Through systematic evaluation research and analysis,MXGSD has a certain effect on the treatment of asthma with two different phenotypes such as bronchial asthma and cough variant asthma,especially the combination of MXGSD and western medicine in the treatment of adult or pediatric bronchus compared with western medicine,asthma has a significant improvement in efficiency.It can improve lung function(FEV1,FEV1%,PEF),EOS level,and the number of acute attacks in 12 months after treatment in adult.And it can improve the scores of the main symptoms and signs and the ACT score in children.The clinical dose is Mahuang 6g,Xingren 9g,Gancao 6g,Shigao 30g.The commonly used drugs in clinical practice are huangqin,beimu,chantui,jiegeng,sangbaipi,jiangcan,dilong,pipaye,gualou,suzi,banxia,shegan.However,because the evaluation of this system is limited by the methodological quality and the number of studies,and the level of clinical evidence is low,more and more high-quality,large-sample in-depth research is needed.2.Through network pharmacology research and analysis,MXGSD may regulate the body's overall neuro-immune-inflammatory response by participating in gene expression,transcription,etc.,to treat asthma.Among them,neurotrophin,estrogen,and PI3K-Akt signaling pathway may be the main mechanism of action of MXGSD in the treatment of asthma.Among them,PI3K-Akt signaling pathway,estrogen signaling pathway,and platelet activation may be the main signaling pathways that reflect the Junchen Zuoshi meaning of MXGSD3.Through animal experiment research and analysis,the different Junchensuo compound of MXGSD has different intervention effects on asthmatic rats,especially in terms of general prescriptions,body weight,asthmatic latency,behavioral evaluation,EOS count,IgE level,IL-4level,IFN-y level,HE staining of lung tissue,PI3K mRNA expression level and AKT mRNA expression level.However,overall,the efficacy of the whole party is more obvious than that of other different compatibility decomposed parties,suggesting that the Junchen Zuoshi of Chinese herbal compound has a certain synergistic effect.Moreover,the PI3K-Akt signaling pathway is related to the synergistic effect of the compound Junchenzuoshi in the treatment of asthma.