| Objective:1)Observing and evaluating the clinical efficacy of Wenfei Xiaozhang granules(WXG)in the treatment of patients with stable chronic obstructive pulmonary disease(COPD)(with the pattern of deficiency of both the lungs and kidneys);2)By observing the regulation of macrophage polarization in a rat model of COPD by WXG,the mechanism of action of WXG in the treatment of COPD was partially elaborated to provide experimental basis for the clinical application of WXG.Methods:1.Clinical research: 120 patients diagnosed with mild,moderate,and severe COPD in Western medicine and exhibiting symptoms of lung and kidney deficiency in traditional Chinese medicine(TCM)were randomly assigned to either a treatment or control group.Both groups received conventional Western medicine treatment for COPD,with the treatment group additionally receiving WXG.Outcome measures included TCM diagnostic indicators,lung function tests,6-minute walk-test,dyspnea index,CAT scale scores,serum inflammatory markers,and safety parameters.Data collection occurred before and after a 4-week treatment period.Statistical analysis will compare outcomes between groups.2.Experimental research:1)SPF grade,weighing 180g-200 g,60 male SD rats were divided into 6 groups,including blank group,model group,dexamethasone group(DXM),WXG low dose group(WXG-L),WXG middle dose group(WXG-M),WXG high dose group(WXG-H)and so on,with 10 rats in each group by using randomized numerical table method.The COPD rat model was established by applying intra-airway droplet lipopolysaccharide(LPS)combined with cigarette smoke modeling method in all groups except the blank group.2)From the first day to the 30 th day of the experiment,the low,medium and high dose groups and the DXM group were treated by gavage,and the rats in the blank group were kept normally without any intervention.3)Lung function test system for each group of rats.Pathologic sections were taken to observe the histopathologic morphology of the treated lungs.4)Determination of serum IL-8,IL-1β and IL-10 levels in rats using ELISA.5)RT-q PCR,Western-blot,and immunofluorescence techniques were used to observe the changes of macrophage polarization markers in each group of rats after treatment.Result:1.Clinical research: There were no statistical differences in gender,age,height and weight between the two groups of patients in the treatment and control groups(P >0.05),and both groups were balanced at baseline.The total effective rate of the treatment group was higher than that of the control group(P < 0.05).The treatment group reduced the TCM evidence score(P < 0.05),dyspnea score(P < 0.05),quality of life score(P < 0.01),and increased the 6-minute walking distance(P < 0.01)compared with the control group.No significant adverse reactions were observed in both groups throughout the treatment.2.Experimental research: HE staining of pathological sections showed a certain degree of recovery of the histopathological structure of the lungs of the treated rats and a reduction of inflammation.Compared with the blank group,peak inspiratory flow(PIF),peak expiratory flow(PEF),and expiratory mid-expiratory flow(EF50)were significantly decreased in rats in the model group(P < 0.001).Compared with the model group,the serum levels of IL-8 and IL-1β were decreased and IL-10 was increased in the rats in the WXG-L,WXG-M and WXG-H groups and the DXM group.Compared with the model group,the lung tissue CD86 m RNA expression level of rats in the WXG-M and WXG-H groups and the DXM group was decreased(P < 0.05,P < 0.01,P < 0.01),the lung tissue i NOS m RNA expression level of rats in the WXG-H group and the DXM group was decreased(P < 0.01),and the lung tissue of rats in the WXG-M and WXG-H groups and the DXM group Arg-1 m RNA expression level increased(P < 0.01,P < 0.001,P < 0.001).Compared with the model group,CD86 protein expression level in the lung tissue of rats in the WXG-M and WXG-H groups and the DXM group was decreased(P<0.01,P<0.001,P<0.001),i NOS protein expression level in the lung tissue of rats in the WXG-L,WXG-M and WXG-H groups and the DXM group was reduced(P<0.05,P<0.01,P<0.001,P<0.001),and Arg-1 protein expression level in the lung tissue of rats in the WXG-L,WXG-M and WXG-H groups and the DXM group was increased(P<0.05,P<0.001,P<0.001),and Arg-1 protein expression level in the lung tissues of rats in the WXG-L,WXG-M and WXG-H groups and the DXM group was increased(P < 0.05,P <0.001,P < 0.001,P < 0.001,P < 0.001).Immunofluorescence results showed that compared with the model group,the expression of CD86 in rat lung tissues was significantly lower in the WXG-L,WXG-M,and WXG-H groups and the DXM group(P<0.01,P<0.001,P<0.001,P<0.001),and the expression of i NOS in rat lung tissues in the WXG-M,and WXG-H groups and the DXM group(P<0.001),and the expression of Arg-1 in rat lung tissues was significantly higher in the WXG-L,WXG-M and WXG-H group,and DXM group,the expression of Arg-1 in rat lung tissue was elevated(P < 0.05,P< 0.001,P < 0.001,P < 0.001,P < 0.001).Conclusion:1.The efficacy of WXG combined with western medicines in the treatment of lung and kidney deficiency evidence of COPD in the stable stage is clear and superior to the treatment with western medicines alone.WXG can alleviate respiratory distress,increase exercise endurance,and improve the quality of life of patients.2.WXG can inhibit the lung histopathological process of COPD rats;the serum IL-8and IL-1β content of rats in the WXG-L,WXG-M and WXG-H groups decreased compared with that of the model group,and the IL-10 content increased compared with that of the model group,which can reduce the degree of serum inflammation in COPD rats.3.WXG can reduce the expression of M1-type macrophage polarization markers CD86 and i NOS and increase the expression of M2-type macrophage polarization marker Arg-1 in lung tissues,regulate the balance of M1/M2 polarization,and attenuate inflammatory responses,thus playing a therapeutic role in the disease process of COPD. |
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