Exploring The Anti-asthma Mechanism Of Shegan Mahuang Decoction Based On The MyD88/IKK/NF-κB Pathway And Its Clinical Study On Treating Cold Asthma In Children

Objective:1.Experimental study:an ovalbumin（OVA）-induced rat model of asthma was established and treated with Shegan Mahuang Decoction（SMD）,and the anti-asthma mechanism of SMD was discussed based on multi-omics techniques.2.Clinical research:evaluating the clinical efficacy of SMD in the treatment of cold asthma in children objectively,and providing scientific basis for the clinical application of SMD.Methods:1.Experimental study:72 rats were randomly divided into 6 groups,contained the normal group（Control group）,OVA-induced group（Model group）,the high,medium,and low dose groups of SMD（SMD-H,SMD-M,SMD-L groups）,and the dexamethasone group（Dex group）,with 12 rats in each group,OVA-induced rat models were established in all groups except for the Control group.The SMD-H,SMD-M,and SMD-L groups were given different doses of SMD,the Dex group were given dexamethasone tablets,and the Control and Model groups rats were given corresponding distilled water.The levels of serum immunoglobulin E（IgE）,interleukin-4（IL-4）,interleukin-6（IL-6）,and C-reactive protein（CRP）were detected by enzyme-linked immunosorbent assay（ELISA）.Hematoxylin-Eosin（H&E）staining was used to observe the pathomorphological changes of rat lung tissue in each group,and the airway inflammation scores was performed.The biomarkers and differentially expressed proteins（DEPs）in rat lung tissue were selected based on the metabolomics（LC-MS）and proteomics（TMT）,and the signal transduction pathway of SMD in the treatment of asthma was explored by comprehensive analysis method of the multi-omics.The expression levels of MyD88,IKK（α）,P-NF-κB（p65）,NF-κB（p65）,P-IκBαand IκBαof rat lung tissue in each group were detected by Western blotting（WB）.2.Clinical research:66 children with cold asthma were selected and randomly divided into the control group and the experimental group,with 33 cases in each group.The control group were treated with Budesonide Suspension for Inhalation;the experimental group were treated with SMD on this basis.Comparing the traditional Chinese medicine（TCM）syndrome scores,the concentration of fractional exhaled nitric oxide（Fe NO）and pulmonary function test indexes[the percentage of peak expiratory flow rate（PEF%）,the percentage of forced expiratory volume in the first second（FEV₁%）,forced vital capacity（FVC）,1 second rate（FEV₁/FVC）]before and after treatment and the clinical total effective rate of two groups.Results:1.Experimental study:the levels of IgE,CRP,IL-4,and IL-6 in the Model group increased prominently in comparison with the Control group;the levels of IgE,CRP,IL-4,and IL-6 in the SMD treatment groups also decreased with statistical significance（P<0.05）.There was a serious infiltration of inflammatory cells into the surrounding blood vessels and connective tissue,narrowing of the bronchial lumen,and mucosa thickening in the OVA-induced lung tissue of the Model group rats;the OVA-induced pathological changes were obviously improved after the treatment of SMD,and the increasing score of the Model group was reduced dose-dependently via SMD treatment.There were 34 biomarkers and 84DEPs screened from rat lung tissue,which were mainly associated with lipid metabolism,lysosome/phagosome pathway,and nicotinamide adenine dinucleotide phosphate（NADPH）oxidase and its product of reactive oxygen species（ROS）mediated oxidative stress.the protein expressions of MyD88,IKK（α）,P-NF-κB（p65）,NF-κB（p65）,P-IκBα,and IκBαin the Model group are higher than that in the Control group（P<0.05）,which show a decreasing trend after treatment with SMD（P<0.05）.2.Clinical research:the TCM syndrome scores of children in two groups were reduced in different degrees after treatment,and the TCM syndrome scores of the experimental group were significantly lower than the control group（P<0.05）.After treatment,the concentration of Fe NO in both groups of children were decreased in different degrees,and the Fe NO concentration in the experimental group was lower than that in the control group（P<0.05）.Pulmonary function was improved in both groups of children in different degrees after treatment,the PEF%,FEV₁%,FVC,and FEV₁/FVC in the experimental group were higher than those in the control group（P<0.05）.The clinical total effective rate of the experimental group was significantly higher than the control group（P<0.05）.Conclusion:1.Experimental study:SMD can reduce airway inflammation and improve airway remodeling by regulating MyD88/IKK/NF-κB signaling pathway,and then achieving the purpose of treating asthma.2.Clinical research:treating children of cold asthma with SMD can alleviate the clinical symptoms of children,improve pulmonary function,reduce the level of airway inflammation and elevate the total clinical efficiency.