Clinical And Experimental Study Of ShenQiBuFeiTang In Treating Stable Chronic Obstructive Pulmonary Disease With Lung-Qi Deficiency Syndrome

Objective:1.To estimate the clinical effects and safety of ShenQiBuFeiTang on stable chronic obstructive pulmonary disease(COPD) patient with lung-Qi deficiency syndrome.2.To observe the effects of ShenQiBuFeiTang on stable COPD rat model with lung-Qi deficiency syndrome and explore the possible mechanisms.Methods:1.Clinical study:A randomized,stratified,single-blind,controlled trial was designed.60 stable chronic obstructive pulmonary disease(COPD) patients with lung-Qi deficiency syndrome in mild or moderate degree were allocated by random number table to therapy group(T,n=30) and control group(C,n=30).The patients received single conventional therapy in the group C and conventional therapy and ShenQiBuFeiTang in the group T for 3 months. Efficacy measures were clinical symptom and acute exacerbation of chronic obstructive pulmonary disease(AECOPD), BODE index,quality of life,lung function and adverse effect in the course of the treatment and after the treatment.2.The experimental study:Make quantitative stimulation with tobacco,SO2 and papin to exposed rat for 60 days to establish stable COPD rat model with lung-QI deficiency syndrome. Sixty male Wistar rats were randomly divided into:normal group (N),model group(M),low dose treatment group (LT),mediumdose treatment group (MT),high dose treatment group (HT),and glucocorticoid treatment group (GCT). The drug administration then followed for 30 days. To observe and record the general status of the rats such as body weight,repiratory frequency,et al;to measure lung function with a small animal plethysmograph;to test the total and differential cell counts in bronchoalveolar lavage fluid(BALF) and the contents of fibronectin(FN) in the BALF by radioimmunoassay; to observe the pulmonary tissue histopathological features by means of HE staining and the view of collagen deposition by means of Masson staining under the light microscope;to measure the thinknesses of the airway wall and smooth muscle layer of the small airway and expression of collagen by means of computer image analyzer; the NF-κB activity and the protein expressions of MMP-9 and TIMP-1 in small brouch and lung tissue were examined by immunohistochemical analysis.Results:1.Clinical study:All analyses were on the basis of per-protocolpopulation.The markedly effective rates were 55.17% and the effective rates were 89.66% in treatment group VS. the markedly effective rates of 23.33%, the effective rates of 66.67% in the control group. The clinical symptoms improvement of the therapy group were better than that of the control group (P＜0.05).The number of the case and the frequency and duration of AECOPD in the therapy group were markedly decreased than those in the control group(p<0.05).After treatment, BODE index, BMI and MMRC scare were remarkably lower than those before treatment in group T, and BODE index, BMI and 6MWT scare were remarkably lower than those in the control group(p<0.05). FEV1% pred and 6MWT scare were not lower than those before treatment in group T(P>0.05).There were not significant difference in FEV1% pred and MMRC scare between group T and group C(P>0.05).The quality of life the total mean score (TMS),general activity score(F1S),social activity score(F2S),depression score (F3S),and anxiety score(F4S) had been improved significantly in the group T(P<0.05), with significantly differences after treatment compared with the group C (P< 0.05).There was a uptrend to FVC、FEV1、FEV1% pred、FEV,/FVC of the group T after treatment, but there were not significant difference as compared with before treatment (P>0.05). There was a downtrend to FVC、FEV1、FEV1%、FEV1/FVC of the group C after treatment, but there were no significant differences as compared with before treatment (P>0.05). There were significant differences in FVC、FEV1、FEV1% pred、FEV1/FVC between the group T and the group C (P< 0.05).In the whole treatment period,there was no change in life signs,ECG,data of laboratory test,adverse effects,and severe adverse effects in the two groups.2.The experimental study:The symptom and syndrome of the M group consisted with TCM clinical symptoms. The M group got the histopathological changes of chronic bronchits and emphysema.The thinknesses of the small airway wall and smooth muscle layer of the M group were significantly increased compared to the N group respectively(p<0.01).Lung percentage of forced expiratory volume in first 0.3 second to forced vital capacity(FEV0.3/FVC%) of the M group was lower than the N group (＜0.01).Lung inspiratory resistance(Ri) and expiratory resistance(Re) of the M group were higer than the N group (<0.01).The lymphocytes and the macrophages of the M group in BALF increased.The contents of fibronectin(FN) in the BALF,the expressions of collagen and the NF-κB activity and the protein expressions of MMP-9 and TIMP-1 in small brouch and lung tissue of the M group were significanthly higher than those of the N group(p<0.01).After treatment, the changes of lung function in the HT, MT, and GCT group were markedly better than those in the M group(p<0.01).The contents of fibronectin(FN) in the BALF and the expressions of collagen in the HT, MT group were remarkably decreased than those in the M group (p<0.01). The thinknesses of the airway wall and smooth muscle layer of the small airway were remarkably lower in the HT group than those in the M group(p<0.05). The area and number of alveolus in the HT, MT, LT and GCT group were not changed as compared with the M group. The NF-κB activity and the protein expressions of MMP-9 in the HT, MT and GCT group were lower than those in the M group(p＜0.01), the GCT group was better than the HT, MT group.The protein expressions of TIMP-1 in the HT, MTgroup were lower than those in the M group (P＜0.01),and those in the GCT group were not changed as compared with the M group (P>0.05).Conclusion:1.Clinical study:The management of the conventional therapy associated with ShenQiBuFeiTang could improve the symptoms,quality of life,reduce AECOPD, stabilize lung function,and stay exacerbation of COPD significantly compared with the single conventional therapys on stable COPD patient with lung-Qi deficiency syndrome. ShenQiBuFeiTang may be beneficial and safe in treatment of stable COPD. 2.The experimental study:The change TCM of clinical symptoms,pathology,lung function and chronic airway inflammation accorded with those of stable COPD patient with lung-QI deficiency syndrome.The NF-κB may play an important pathogenetic role in the airway remodeling of stable COPD with lung-Qi deficiency syndrome,with regulating the expression of MMP-9 and directly/indirectly involving in the proliferation of the airway smooth muscle cell(ASMC) of the small airway.ShenQiBuFeiTang can cure COPD efficiently and stay lung function from dropping, might influence airway remodeling by downregulating activity of NF-κB and the expression of MMPs and regulating the balance of MMP-9 /TIMP-1,and reducing the proliferation of the airway smooth muscle cell. The effect of ShenQiBuFeiTang on NF-κB may partly influence the expression of MMP-9.