| Research purposesThrough the clinical research and experimental research on the treatment of COPD by TL,the effectiveness and mechanism of TL in the treatment of COPD were comprehensively evaluated and analyzed.?1?Randomized,double-blind,single-dummy,parallel,placebo-controlled,multi-center clinical trial was conducted to investigate the effect of Long Kechuanling Capsule on the improvement of symptoms,lung function,CAT scores,and quality of life of patients with chronic obstructive pulmonary disease.effect.To evaluate the effectiveness and safety of Tianlong Kechuanling in the treatment of chronic obstructive pulmonary disease during its stable phase.?2?To analyze the compound of TL by TCMSP to explore its pharmaceutical chemical constituents,Predict the types and effects of their treatment of disease,targets and signaling pathways.The purpose of this paper is to analyze the system of TL by means of the pharmacological network of traditional Chinese medicine,and to systematically analyze and interpret TL to predict the molecular mechanism of drug treatment of COPD.?3?In this study,high-throughput sequencing method was used to study the bioinformatics of transcriptome of lung tissue in rats with COPD after TL,in order to make a more systematic and comprehensive evaluation Tianlongkechuan Ling mechanism of action for the follow-up study to identify the direction.Research methods?1?Randomized,double-blind single-simulations,placebo-controlled parallel,multicenter clinical trial.Several 92 patients with stable COPD were screened in multiple research centers and randomly divided into TL group and placebo group TL.TL group were given TL.placebo group were given placebo.Three months after treatment,the main indexes of pulmonary function in patients with COPD?FVC,FEV1,FEV1%,FEV1/FVC?,COPD?CAT?score,Expectorant parameters integral and expectorant efficacy,cough symptom scores and cough treatment efficacy,dyspnea classification?mMRC?score and dyspnea efficacy,TCM symptom score and the effect of traditional Chinese medicine symptoms.?2?The traditional Chinese medicine system pharmacology database and analysis platform?TCMSP?TL effective components and mechanism of screening and evaluation.Using the functions of the TCMSP database for the detection of herbal ingredients and their toxicokinetics properties,the potential bioactive components of TL and their human Oral bioavailability,half-life,drug similarity,Caco-2 permeability,blood-brain barrier and Lipinski's rule?LR?.Pharmacological analysis of the constituents according to LR,OB and DL.Bioinformatics analysis was performed using the first BATMAN-TCM,an online bioinformatics analysis tool designed specifically for the study of TCM molecular mechanisms.To predict the main effective chemical composition of TL onset,the main role of these chemical agents,TL may treat the disease and other information.?3?In this study,COPD rat model was duplicated by smoked and tracheal instillation of lipopolysaccharide?LPS?,and 85 SD rats were randomly divided into normal control group,COPD model group,TCM group,Pineal group,combined group,from the day of modeling intragastric administration,medication time for a total of 3 months.Pulmonary function was measured by using BUXICO,after the animals were sacrificed,the pathological changes of lung tissue were observed by HE staining,the bronchoalveolar lavage fluid?BALF?TNF-?and IL-8 in the lung tissue of rats were detected.In addition,the RNA in rat lung tissue was extracted,the original sequencing sequence was constructed and the library was checked,and the differentially expressed genes were screened.KEGG enrichment analysis,in addition,the normal control group and the COPD group,COPD group and Denon two sets of differential gene data selected the same and up-down regulation of the key genes for further analysis.Result?1?TL treatment of COPD in stable?lung deficiency syndrome?randomized,Double-blind single simulation,Placebo parallel control,Multi-center clinical trialA total of 108 patients were enrolled in the three pilot centers,and a total of 92 patients completed the study.8 cases of exfoliated cases due to various reasons during the treatment of acute exacerbation of COPD complications need to be treated with other drugs and methods,6 patients were unable to take drugs because of the need to be removed,the other two patients reluctant With the completion of the relevant inspection and removed.Of the108 patients,33 were from the First Affiliated Hospital of Guangzhou Medical University,28 were from the Guangzhou Traditional Chinese Medicine Hospital,and 31 were from Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine.The general situation,The lung function was not statistically significant,comparable.After the experiment,we found:?1?The main indexes of lung function:FVC,FEV1and FEV1%of the placebo group and TL group after the experiment were all statistically significant?P<0.05?Value,FEV1 value,FEV1%were statistically significant?P<0.05?.?2?CAT score of COPD?CAT?score was significantly higher in experimental group than that in TL group?P<0.05?,CAT value in TL group had statistical difference before and after the experiment?P<0.05??3?Cough symptom score and cough curative effect:After the experiment,the score of cough symptom score and cough in the placebo group and the TL group were significantly different?P<0.05?,The score of cough symptom score and cough in the TL group before and after the experiment?P<0.05?.?4?The effect of expectorant score and expectorant expectoration:There was significant difference between expectorant and expectorant in placebo group and TL group?P<0.05?There was significant difference?P<0.05?between expectorant score and expectorant efficacy before and after treatment?P<0.05?,?5?There was significant difference between the placebo group and TL group on dyspnea classification and dyspnea?P<0.05?The difference of dyspnea classification and dyspnea between the two groups before and after the experiment was statistically significant?P<0.05?,?6?Compared the TCM symptom score and TCM symptom scores between the placebo group and the TL group after the experiment A Difference meter?P<0.05?,TL patients before and after the experimental group symptom scores and compare the efficacy of TCM symptoms statistical difference?P<0.05?.No safety problems due to taking TL were found in the experiment.?2?Exploring the Mechanism of TL in Treating COPD Based on Network PharmacologyWe obtained 1258 kinds of chemical constituents from Tianlong Kechuanling Capsule by TCMSP.From these 1258 chemical constituents there are 80potentially effective ingredients which meet all the criteria were selected based on LR,OB and DL.After bioinformatics analysis of these compounds by BATMAN-TCM,a total of 145 KEGG Pathways were obtained,of which 29 were significantly enriched KEGG Pathways.After further screening,36 biological processes,10 cellular components were obtained,and 7 molecular functions were obtained.Based on the OMIM database,188 potential treatments for Tianlong Kechuanling Capsule were predicted.Based on TTD database,30potential treatments for Tianlong Kechuanling Capsule were predicted.?3?Transcriptional bioinformatics study of TL on COPD rat modelIn this experiment,rats in the COPD model group quiescently accumulated fur,experienced slow weight gain,frequent breathing,frequent cough,decreased lung function,and a large number of IL-8 and TNF-?expression.Pathological tissue showed significant inflammatory cell infiltration.Airway mucosal edema,increased mucus secretion,localized emphysema,and stenosis of the air cavity suggest pathological models of COPD rats.From the general condition of rats and body weight,pulmonary function test,inflammatory index detection and histopathological analysis,it was shown that Tianlong Kechuanling can effectively improve the general condition of rats and improve lung function such as Cdyn,FRC,PEF,FEV0.3/FVC.The index,which reduced the exudation of inflammatory cytokines IL-8 and TNF-?in the rat alveoli,alleviated some of the pathological lesions,reduced airway dilatation,decreased inflammatory cell infiltration,and reduced airway mucosal edema.After the RNA library was constructed,sequencing analysis revealed that there were 27 genes in the COPD group and the TL group for difference and annotation.Among them,there are 13 up-regulated genes and14 down-regulated genes.KEGG metabolic pathway enrichment found that relative to the COPD group,the TL group was significantly enriched in antigen processing and performance,chemokine signaling pathways,and Toll-like receptor signaling pathways.Conclusion?1?The short-term use of Tianlong Kechuanling capsules did not significantly improve the lung function of patients with COPD.Although individual indicators have an increasing trend,it is also necessary to increase the sample size to continue verification.Tianlong Kechuanling Capsule can improve the quality of life of patients with COPD.Tianlong Kechuan Ling can improve the clinical manifestations of dysentery,sputum adhesion and dysentery in COPD patients,and increase the comfort of patients.Tianlong Kechuanling has a good antitussive effect.Tianlong Kechuanling Capsule can effectively relieve airway obstruction and reduce the difficulty of breathing in patients.Tianlong Kechuanling can also improve the clinical symptoms such as spontaneous sweating,bad wind,fatigue,poor appetite,abdominal distention,loose stools,etc.that are often seen in patients with COPD.In a word,Tianlong Kechuanling Capsule can effectively and effectively alleviate the clinical symptoms of patients with COPD from multiple angles,improve the comfort and quality of life of patients,and is worthy of clinical application.?2?Based on internet pharmacology technology,Tianlong Kechuanling was found to have the characteristics of“multi-component,multi-target,multi-pathway”.According to the results of network pharmacology,Tianlong Kechuanling may act mainly through drug target CACNA1C.,ARRB2,ADRA1A,ADRA1B,ADRA1C,HTR2A,HTR2B,HTR2C and CHRM2 regulate MAPK signaling pathway,chemokine signaling pathway,TRP channel inflammatory mediator regulation,vascular smooth muscle contraction pathway,MAPK signaling pathway and PI3K-Akt signaling pathway To anti-oxidative stress,regulate inflammatory response,inhibit pulmonary vascular smooth muscle contraction,anti-apoptosis effect.?3?In this study,the high-throughput sequencing method was used to study the transcriptome bioinformatics of the lung tissue of rat model of chronic obstructive pulmonary disease treated with Tianlong Kechuanling.It was found that Tianlong Kechuanling can improve COPD.General situation of rats,improve Cdyn,FRC,PEF,FEV0.3/FVC and other lung functions,reduce the expression of IL-8 and TNF-?,improve lung tissue inflammatory cell infiltration in COPD rats,airway mucosal edema,increased mucus secretion,Localized emphysema,air cavity stenosis and other pathological manifestations.Tianlong Kechuanling is mainly controlled by Hsp90aa1,Pf4,CXCL10,Ifit1 and other target genes,through antigen processing and signaling pathways,chemokine signaling pathways,Toll-like receptor signaling pathway,to patients with chronicobstructivepulmonarydisease.Toimmuneregulation,anti-inflammatory,anti-virus,anti-platelet and anticoagulant effects. |
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