| Research purposes:1?Based on molecular docking technology,explore the mechanism of Qingfei Litan Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD).2?To explore the protective effect and mechanism of Qingfei Litan Decoction on rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).3?Randomized?single blind clinical trial was conducted to investigate the effect of Qingfei Litan Decoction on the clinical symptoms and the blood gas analysis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Research methods:1?Obtain the chemical constituents from Qingfei Litan Decoction from the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and then screen according to Lipinski's rule(LR),drug similarity(DL)and oral bioavailability(OB)characteristics.The effective chemical composition of the lungs was cleared out and the three-dimensional structure was obtained in the TCMSP database and analysis platform.The Discovery Studio 4.5 and AutoDock Vina Molecular Docking Software were used to construct a receptor target associated with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to determine its spatial coordinates.It is then docked with the effective chemical components in the Chinese herbal compound after screening and treatment.2?50 rats were randomly divided into normal control group,model control group,Qingfei Litan Decoction large,medium and small dose groups.Except the normal control group,the other 4 groups were established with a AECOPD model by instilling lipopolysaccharide with a smoked air tube.Qingfei Litan Decoction large,medium and small dose groups were given 8g/kg,4g/kg and 2g/kg on the 2nd to 13th day of the experiment,15~30 days respectively.The normal control group and the model control group were respectively Give the same volume of purified water by gavage.The course of treatment for the 5 groups of rats was 4 weeks.At the end of the experiment,the lung function of each group was measured.The venous blood was taken to measure IL-8 and TNF-a.The left lung tissue was taken to measure the content of MDA and SOD in lung tissue.The right lung tissue was taken to measure MMP-9,TIMP-1 and JAK.-1,mRNA and protein expression levels of STAT-3.3?Randomized?single blind clinical trial was conducted,Sixty hospitalized AECOPD patiens with phlegm-heat and blood stasis syndrome in the lung in TCM are randomly divided into two groups:the trial group and the control group.The patiens of the control group accept conventional therapy of the western medicine(controllability oxygen treatment,bronchodilatora,antibiotic,expectorants),The patients of trial group take the Chinese medicine decoction(Qingfei Litan Decoction),and simultaneously accept conventional therapy of the western medicine.The period of treatment is 10 days.To compare the result of two groups by analyzing clinical aymptom and the blood gas analysis.Result:1?According to the TCMSP database and analysis platform,a total of 1258 chemical components were obtained from Qingfei Litan Decoction.After screening by LR,DL and OB characteristics,there are 56 effective chemical components,including 3 melons,29 astragalus,5 in Fritillaria,5 in Houttuynia,10 in almonds,and 1 in Campanulaceae.Three,and according to literature research,obtained three effective chemical components in Qingtiankui.Through molecular docking technology,it was found that the 56 effective chemical components selected were successfully docked with 3QXY,and 38 of them had an RMSD of ?0.2 nm after docking with 3QXY.All of the 56 chemical components were successfully docked with 4IW0,and 23 of them had an RMSD of ?0.2 nm after docking with 4IW0.23 of the 56 chemical components were successfully interfaced with 5NBU,and 16 of them were effective to interface with 5NBU with an RMSD of ?0.2 nm.2?(1)The FVC,FEV 0.3,FEV0.3/FVC and PEF in the middle dose group of Qingfei Litan Decoction group were significantly increased(P<0.05),and the large dose group of Qingfei Litan Decoction was large.Rat FVC,FEV 0.3,FEV0.3/FVC and PEF were significantly higher than the middle dose group(P<0.05).(2)IL-8 and TNF-a were significantly decreased in the lower dose group of Qingfei Litan Decoction group(P<0.05),and IL-8 and TNF-a in Qingfei Litan Decoction group.Both were significantly lower than the middle dose group(P<0.05).(3)The MDA of the lung tissue of Qingfei Litan Decoction group was significantly lower than that of the normal control group,and the SOD was significantly increased.The difference was statistically significant(P<0.05).The Qingfei Litan Decoction high-dose group rats The MDA of lung tissue was significantly lower than that of the normal control group,and the SOD was significantly increased,the difference was statistically significant(P<0.05).(4)The expressions of MMP-9,JAK-1 and STAT-3 mRNA in the lung tissue of Qingfei Litan Decoction group were significantly lower in the lower dose group,and the TIMP-1 mRNA in the lower dose group was significantly increased(P<0.05).The expressions of MMP-9,JAK-1 and STAT-3 in the lung tissue of Qingfei Litan Decoction group were significantly lower than those in the middle dose group,and TIMP-1 mRNA was significantly higher than the middle dose group(P<0.05).(5)The MMP-9,JAK-1,p-JAK-1,p-STAT-3 and STAT-3 proteins in the lung tissue of Qingfei Litan Decoction group were significantly lower in the lower dose group,TIMP-1 The protein was significantly increased in the lower dose group(P<0.05);the MMP-9,JAK-1,p-JAK-1,p-STAT-3 and STAT-3 proteins in the lung tissue of the Qingfei Litan Decoction high dose group Both were significantly lower than the middle dose group,and the TIMP-1 protein was significantly higher than the middle dose group(P<0.05).3?The patients of trial group have notable amelioration at clinical symptom and signs such as cough,expectoration,asthma and chest pains after treatment(P<0.01).the symptom of anorexia did not differ after treatment(P>0.05).The patients of trial group have notable amelioration at clinical symptom and signs such as cough,expectoration,asthma and chest pains compared with control group(P<0.05or<0.01),The results show the curative effect on clinical symptom and signs such as cough,expectoration,asthma and chest pains in trial group was excelled that in control group.After 1 course of treatment(10 days),The patients of trial group have notable amelioration at syndrome score after treatment(P<0.01);The patients of control group also have notable amelioration at syndrome score after treatment(P<0.01);The patients of trial group have notable amelioration at syndrome score after treatment compared with control group(P<0.05),The results show the curative effect on syndrome score in trial group was excelled that in control group.Conclusion:1?The method of molecular docking to study the multi-target material basis of traditional Chinese medicine compound was applied to the study of Qingfei Litan Decoction.The results showed that Qingfei Litan Decoction reflects the characteristics of multi-component,multi-target and multi-channel of traditional Chinese medicine.It contains a variety of chemical components that can simultaneously act on AECOPD-related targets for controlling inflammatory responses,regulating oxidative stress gene expression,and protease/anti-protease system imbalances,thereby achieving the goal of treating AECOPD.The results preliminarily explained the multi-target mechanism of Qingfei Litan Decoction in the treatment of AECOPD,which provided a direction for the subsequent experimental study of Qingfei Litan Decoction,and also had a certain guiding effect on the follow-up development of this compound.2?Qingfei Litan Decoction can significantly improve the lung function of rats with acute exacerbation of chronic obstructive pulmonary disease and heat-stasis syndrome,and reduce blood IL-8 and TNF-?,reduce lung tissue MDA and increase SOD,regulate JAK1/STAT3 The pathway is associated with MMP9/TIMP1 expression.3?Qingfei Litan Decoction is effective in the treatment of AECOPD patiens with phlegm-heat and blood stasis syndrome in the lung in TCM with conventional therapy of the western medicine. |
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