| This study includes theoretical discussion,clinical research and experiment research.Theoretical discussionComprehensive TCM theories of collateral disease,mass and assembling and dispersing,we believe that the pathology of COPD,airway remodeling,is consistent with pathological features of COPD," pulmonary collateral micro Zhengjia",and put forward to Yiqi Huoxue Xiaozheng Decoction,the representative prescription of treatment principle of Yiqi Huoxue Xiaozheng Tongluo,which is adjusting the balance of assembling and dispersing.TGF-β1/smad signaling pathway is one of the main pathway promoting abnormal deposition of extracellular matrix which leads to airway remodeling.And it is consistent with the forming process of the "pulmonary collateral micro Zhengjia".On this basis,we believe that adjusting the TGF-β1/smad signaling pathway to delay airway remodeling is the key target of Yiqi Huoxue Xiaozheng Decoction.This not only provides modern molecular biological evidence for traditional Chinese medicine,but also disprooves the rationality of the pathogenesis hypothesis of "pulmonary collaterals micro Zhengjia".The clinical researchObjective:To explore the clinical effect of Yiqi Huoxue Xiaozheng Decoction on stable chronic obstructive pulmonary disease patients and its regulation effect of TGF-β1/smad signaling pathway.Methods:According to the inclusion and exclusion criteria,60 stable COPD patients were randomly assigned to the treatment group and the control group,each group had 30 patients.The control group was given conventional western medicine treatment,the treatment group was given conventional treatment of western medicine combined with Yiqi Huoxue Xiaozheng Decoction.The patients were treated for 2 months and followed up for 1 month.Before the treatment,a detailed of patients’ age,sex,occupation,height,weight,smoking history,other diseases,drug use and blood routine,liver and kidney function and other safety indicators should be recorded.Before treatment and 4 weeks,8 weeks and 12 weeks after treatment,record the main symptoms,TCM syndromes and the table(CAT,mMRC)and SpO2 of patients.Before treatment and 8 weeks after treatment,record 6MWT.8 weeks after treatment,patients’ blood should be taken to detect the related proteins of TGF-βl/smad signaling pathway.At last,according to the corresponding evaluation criteria,the clinical efficacy and mechanism of Yiqi Huoxue Xiaozheng Decoction were analyzed.Results:The treatment group(n=28)and the control group(n=27)were involved 55 cases in all.Before treatment,the treatment group and the control group were consistent and comparable.(1)general situation:the control group,male accounted for 18(66.67%),female accounted for 9(33.33%),69.6±7.50 years old,weight was 65.33±11.85kg,height was 162.03±7.94cm,BMI was 24.83±3.73,systolic blood pressure was 128.17±6.88mmHg,diastolic blood pressure was 86.00±6.75 mmHg,respiratory rate was 18.9±1.06 beats/min,heart rate was 76.97±6.54 beats/min,smoking index was 298±370.80,11 cases of smokers(40.74%),16 cases of non-smokers(59.26%),16 patients(59.26%)with non high risk occupation,13 patients(40.74%)with high risk occupation.The treatment group,male accounted for 19(67.86%),female accounted for 19(32.14%),67.83±6.77 years old,weight was 65.89±10.63kg,height was 163.39±7.52cm,BMI was 24.71±3.70,systolic blood pressure was 128.83±7.62mmHg,diastolic blood pressure was 83.50±6.04 mmHg,respiratory rate was 18.73 ± 0.98 beats/min,heart rate was 80.03±6.52 beats/min,smoking index was 202.79±234.32,12 cases(42.86%)of smokers,16 cases(57.14%)of non-smokers,15 cases(53.57%)with non high risk occupation,13 cases(46.43%)with high risk occupation.A total of 55 patients,male accounted for 37(67.27%),female accounted for 18(32.73%),the incidence of male is higher than female,the patients less than 60 years old accounted for 9.09%,61-70 years old accounted for 54.55%,71-80 years old accounted for 36.36%,most patients were elder than 60 years old for smokers,23 cases(41.81%)were smokers,32 cases(58.18%)were non-smokers,the majority of patients did not smoking,31 cases(56.36%)with non high risk occupation,24 cases(43.64%)with high risk occupation,more patients had non high risk occupation.(2)the examination,the table,symptom score,6MWT and SpO2 before treatment:the control group and the treatment group patients’ the blood routine,liver and kidney function were in normal range.Two groups of patients’ blood routine,liver and kidney function,lung function and severity classification,the symptom scores,CAT,mMRC,6WMT and SpO2 were balanced(P>0.05).(3)Efficacy comparison:the control group,4,8 and 12 weeks after treatment decreased gradually and there were significant differences(P<0.05)in the total score,lung qi deficiency,spleen qi deficiency,and kidney qi deficiency,phlegm scores comparing with these before treatment.Compared with mMRC before treatment,there is no significant change(P>0.05)in 4,8 and 12 weeks after treatment.CAT in 4,8,12 weeks after treatment were lower comparing with CAT before treatment and there were statistically significant(P<0.05).6MWT in 8 weeks after treatment was higher comparing with 6MWT before treatment and there was statistically significant(P<0.05).SpO2 in 4,8 and 12 weeks after treatment were higher comparing with it before treatmen and there were significant differences(P<0.05).The treatment group,4,8 and 12 weeks after treatment,decreased gradually and there were significant differences(P<0.05)in the total score,lung qi deficiency,spleen qi deficiency,kidney qi deficiency,blood stasis and phlegm scores comparing with these before treatment.Comparing with mMRC before treatment,mMRC in 4,8 and 12 weeks after treatment were lower and there were significant difference(P<0.05)and the difference d>0.Comparing with CAT before treatment,CAT in 4,8 and 12 weeks after treatment were lower and there were significant difference(P<0.05)and the difference d>2.Comparing with 6MWT before treatment,6MWT in 8 weeks after treatment was higher and there was significant difference(P<0.05).SpO2 in the treatment of 4,8 and 12 weeks were higher comparing with it before treatment and there were significant differences(P<0.05).The scores of main symptoms in the treatment group were lower than it in the control group and there was statistical difference(P<0.05)after 4 weeks treatment.After 8 and 12 weeks treatment,main symptom scores,lung qi deficiency,spleen deficiency,phlegm scores in treatment group were lower than these in the control group and there were statistical difference(P<0.05).The difference of the scores of kidney qi deficiency in the treatment group were higher than it in the control group and there was statistical difference(P<0.05)after 4 and 8 weeks treatment.After 12 weeks treatment,blood stasis scores in treatment group were lower than it in the control group and there were statistical difference(P<0.05).Between two groups,the efficiency of the main symptom score,lung qi deficiency,kidney deficiency scores in the treatment group were higher(P<0.05)after 8 and 12 weeks treatment and the efficiency of spleen deficiency,blood stasis scores were higher(P<0.05)after 12 weeks treatment.But there were no differences in phlegm scores(P>0.05).In the treatment group,mMRC after 12 weeks treatment was lower(P<0.05),while the difference d after 4,8 and 12 weeks treatment were higher(P<0.05).In the treatment group,after 4,8 and 12 weeks treatment,CAT were lower and the difference d were higher,and there were all statistically significant(P<0.05).The difference d of 6MWT after 8 weeks treatment were statistically significant(P<0.05)between the two groups.SpO2 in the treatment groups after 4,8 and 12 weeks treatment were higher(P<0.05).(4)serum factors:in the treatment group,the levels of TGF-β1 and Smad3 were lower,Smad7 was higher comparing with the control group(P<0.05),but there was no significant difference(P>0.05)in the content of Smad2.(5)safety:the control group and the treatment group patients’ blood routine,liver and kidney function were at normal level,and there was no skin rash,itching and other adverse reactions during the whole research.Conclusion:Yiqi Huoxue Xiaozheng Decoction can improve the main symptoms scores,Qi deficiency and blood stasis phlegm syndrome,quality of life and chronic hypoxia of stable COPD patients.Compared with the conventional western medicine treatment,Yiqi Huoxue Xiaozheng Decoction works faster and better.Its mechanism is that reducing TGF-β1,Smad3,and improving Smad7 to regulate TGF-β1/Smad signaling pathway to inhibit the occurrence and development of airway remodeling.The experimental researchObjective:Experiment 1:To establish a COPD rat model which is stable and easy to operate.Experiment 2:To explore the efficacy and mechanism of Yiqi Huoxue Xiaozheng Decoction on COPD rats and provide a molecular basis for "pulmonary collaterals micro Zhengjia" pathogenesis hypothesis and confirm its rationality.Methods:Experiment 1:60 Wistar rats were randomly divided into 1 month blank group,1 month model group,2 months blank group,2 months the model group,3 months blank group and 3 months model group.The model groups received cigarette smoke 1 hour everyday and 3 times(7th,14th,21st days respectively)intratracheal injection of lipopolysaccharide to set up COPD rat model.Every time point groups of rats were measured lung function and take blood and lung tissue to detect corresponding indexes after 1 month,2 months and 3 months.Experiment 2:60 Wistar rats were randomly divided into blank group,model group,western medicine group,low dose group,middle dose group,high dose group.Every group had 10 rats.Except the blank group,all the other groups were done according to the model group rats in Experiment 1.The blank group,the model group and the western medicine group was given 10ml/kg·d saline everyday.At the same time,the western medicine group were given budesonide atomization everyday.The middle dose group rats were given 17.893g/kg Yiqi Huoxue Xiaozheng Decoction.The low dose group and high dose group rats were given 1/2 and 2 as the concentration of The middle dose group rats.After 12 weeks(3 months),the lung function,blood and lung tissue were measured in each group.Results:Experiment 1:The rats in every model group,the general situation of mental,physical state,death and so on were worse and the weight of the model groups were lower than that of the corresponding model group(P<0.05)as time goes by.The pathological changes of airway,alveoli and blood vessels were more in line with the change of COPD after 3 months.There were no significant difference in the FVC of the model groups and the corresponding blank group(P>0.05).The FEV0.3 of the model groups was statistically significant lower than that of the corresponding blank group(P<0.05).The PEF,FEF25%of the 2 months and 3 months model groups were statistically significant lower(P<0.05)than these of the corresponding blank groups.The FEV0.3/FVC,FEF50%,FEF75%,MMF of the 3 months model group were significant lower(P<0.05)than these of the corresponding blank group.The lung function of the 3 months model rats were corresponding with human COPD lung function changes(the obstructive ventilatory disorder).The level of TNF-α,IL-1 β,IFN-γand αl-AT in the model groups rats serum were significantly higher(P<0.05)than those in the corresponding blank groups.The level of NE and TGF-β1 in lung tissue of the 3 months model group were significantly higher(P<0.05)than that in the corresponding blank group.But there was no significant difference(P>0.05)in gene expression of NE and TGF-β1 between the two groups.Experiment 2:The rats in the treatment groups were better than the model group rats in the general situation(mental,physical condition and death and so on).The weight of rats in every group increased with time,the blank group grew fastest,the second is the middle dose group(P<0.05).The middle dose group was better than other treatment group in improving obstructive ventilatory dysfunction(FEV0.3,FEV0.3/FVC%)and small airway index(FEF50%,MMF).The morphology of lung tissue,the western medicine group,the middle dose group and the high dose group were better than the model group and the low dose group.The results of immunohistochemistry showed that the expression of TβRⅠin every treatment group was significantly lower(P<0.05)than that in the model group.Western blot results show:TGF-β1,Smad3 protein in lung tissue of every treatment group rats were lower than the model group(P<0.05).Smad6 in lung tissue of the middle dose group decreased most significantly in the Chinese medicine groups.TGF-β1,Smad2,Smad3,P-Smad2,P-Smad3,Smad4 and Smad7 protein decreased gradually as the Chinese medicine concentration elevate.However,there were no significant differences(P>0.05)in the gene expression of TGF-β1,TβRⅠ,TβRⅡ,Smad2,Smad3,Smad4,Smad6,Smad7 and α-SMA in every group.Conclusion:Experiment 1:Expose to cigarettes smoke 3 months combined with 3 times airway instillation of lipopolysaccharide can establish a more stable COPD rat model which were according with pathological,lung function,inflammatory mediators,cytokines and other aspects of COPD pathogenic process.Experiment 2:Yiqi Huoxue Xiaozheng Decoction can improve COPD rats’ general condition,lung function,airway remodeling by regulating the related proteins on TGF-β1/smad signaling pathway to delay the development of COPD.At the same time,the rationality of "lung collaterals micro Zhengjia" pathogenesis hypothesis was proved. |
PDF Full Text Request