| Objective: This project is intended to JAKs/STATs signal pathway as the research breakthrough point,by observing the effects of LWBQ Capsule on general condition,COPD rat model of pulmonary pathological changes,pulmonary function and inflammatory factor,JAKs/STATs signaling pathway related protein expression and other factors,and the influence of LWBQ Capsule on acute exacerbations of COPD,the number of stable lung qi deficiency patients with syndrome of TCM syndrome score,pulmonary function,verify the effect of LWBQ Capsule on rat model of COPD and COPD in patients with stable stage of lung qi deficiency syndrome,to explore the regulatory mechanism of LWBQ Capsule on JAKs/STATs signal pathway,and to explore the mechanism of the prescription play a role in treatment,so as to provide experimental basis for Chinese medicine prevention and treatment of COPD.Methods:Experimental research:A total of 70 SD rats,then the first adaptive feeding,the rats were randomly divided into normal control(NC)group,model control(MC)group,Jinshuibao(JSB)group,spleen aminopeptidase(PAT)group,low dose of Liuweibuqi(LWBQ low)group,mid dose of Liuweibuqi(LWBQ mid)group and high dose of Liuweibuqi(LWBQ high)group.A total of 7 groups,with 10 rats in each group.Except the rats in the normal group,the drug group rats with lipopolysaccharide instillation of tracheal Nene and processing method for cigarette smoke smoked(CSE+LPS),making COPD model.The rats in group NC and group MC were treated with saline,and the other groups were given the corresponding drugs for the treatment of the stomach.After30 days of treatment,observation and detection of the following indicators: general condition,lung function of rats(FVC,FEV0.3,FEV0.3/FVC),the pathological changes of lung tissue and serum cytokines(IL-4,IFN-?,IL-17)to detect the expression of JAKs/STATs pathway related protein in lung tissue by Western blot the expression of JAK1/p-JAK1,JAK2/p-JAK2,STAT1/p-STAT1,STAT3/p-STAT3,STAT5/p-STAT5 and SOCS1,SOCS3 protein).Clinical research:Clinical observation on the role of LWBQ capsule in the clinical treatment of chronic obstructive pulmonary stabilization.Collect the patients with stable COPD lung qi deficiency 40,were randomly divided into observation group and control group 20,control group was given the basic treatment of Western Medicine(mainly ltdot,Seretide inhalation therapy),the observation group in the control group with LWBQ capsule,the course of treatment for 2 months.The changes of lung function,TCM syndrome score in two groups before and after treatment were observed.According to the observation index and the difference of the observation data,the corresponding statistical processing methods were adopted respectively,and the values were expressed in mean number ± standard deviation((?)±S).Results:Experimental results:1.By intratracheal injection of lipopolysaccharide(LPS)and fumigation,the rat model of chronic obstructive pulmonary disease could be successfully constructed.Smoke smoked for 8 days,the rats appeared cough,asthma and dyspnea and other symptoms,smoked for 23 days,rats had wheezing,throat phlegm and listlessness,bleak color etc..After treatment,NC group had no obvious positive symptoms,rats have normal breathing,good spirit,glossy hair,and an increase in weight;the rats of group MC symptoms did not change significantly,compared with the NC group in the apparent weight loss,increased respiratory rate;After treatment,In the JSB group,PAT group and LWBQ low group,the weight loss and respiration rate were all improved compared with the MC group.LWBQ mid/high rats were significantly better in weight and respiratory rate than MC group.The results showed that LWBQ capsule could improve the general condition and nutritional status of rats.2.LWBQ capsule can relieve the lung function and histopathological inflammatory damage in the rat model of chronic obstructive pulmonary disease and inhibit the release of inflammatory cytokines.According to the results of pulmonary function test(FEV0.3,FVC,FEV0.3/FVC),MC group was significantly lower than that of NC group,suggesting that in a rat model of obstructive ventilation dysfunction.The decrease of lung function in the rats after the administration of gavage to the drug group was significantly better than that in the MC group.LWBQ high group closest to the NC group,LWBQ mid group take second place,but still better than the MC group;In LWBQ groups,The increase of FEV 0.3 and FVC in the LWBQ capsule is closely related to the increase of the dosage of the drug.The results showed that the level of pulmonary function could be improved to some extent after drug treatment,and the airway obstruction and pulmonary ventilation function could be alleviated,but the airway remodeling of COPD could not be reversed.HE pathology can see that in JSB group,PAT group,LWBQ low/mid/high groups cat,bronchial cavity structure was narrow or obliterated,thickening on the wall,emphysema formation,inflammatory cells infiltration and aggregation in lung tissue,alveolar wall thinning,thickening of alveolar septum and other pathological findings.Compared with group MC,the pathological degree of each group was different after treatment.The above pathological findings were improved to varying degrees.Different treatment methods were helpful to improve the typical pathological characteristics of COPD.The LWBQ low/mid/high three groups compared with the MC group,the infiltration of inflammatory cells decreased significantly,and the alveolar septum was less damaged,and had more complete columnar epithelial cells.LWBQ three groups of lung tissue were superior to other treatment groups,including group JSB and PAT.There was a significant increase in inflammatory cell infiltration in the MC group compared with that in the NC group,and the number of inflammatory cell infiltration could be significantly reduced compared to the MC group in LWBQ mid/high group.Compared with the NC group,the content of Il-4 in MC group was significantly lower than that in the NC group,and the level of Il-17 was increased,and the content of IFN-? was significantly increased,suggesting that there was an inflammatory reaction in the rat model of chronic obstructive pulmonary model.Compared with MC group after drug therapy,the content of Il-4 in the plasma of PAT group,LWBQ mid/high group was significantly increased,and the content of IFN-? and Il-17 in LWBQ mid/high group decreased significantly.It is suggested that the LWBQ capsule can inhibit the inflammation by regulating the expression level of il-4 and increasing the expression level of IFN-? and Il-17.3.LWBQ capsule may treat COPD model rats by inhibiting the phosphorylation level of the JAKs/STATs signaling pathway.Using the Western blot to test the results of the pulmonary tissue JAKs/STATs signaling pathways in the lung tissue.Analysis shows that the MC rats compared with NC group,JAK1/p-JAK1,JAK2/p-JAK2,STAT1/p-STAT1 and STAT3/p-STAT3,STAT5/p-STAT5 protein expression significantly increased,SOCS1 and SOCS3 protein expression levels.Using LWBQ capsule treatment,LWBQ low/mid/high groups compared with MC group,of rats JAK1/p-JAK1,JAK2/p-JAK2,STAT1/p-STAT1 and STAT3/p-STAT3,STAT5/p-STAT5 protein expression levels were significantly lower,SOCS1 and SOCS3 protein expression level increased significantly.These results show that the phosphorylation level of the JAKs/STATs signal pathway in the pulmonary tissue of the COPD is significantly increased,and the SOCS signal pathway is suppressed.LWBQ capsule in play a role of anti-inflammatory and treatment,and may be associated with inhibiting JAKs/STATs signal pathway,or by activating negative feedback of JAKs/STATs pathway regulating factor SOCS expressions,thus inhibiting JAKs/STATs signaling pathway phosphorylation level.Clinical findings:1.LWBQ capsule can stabilize the pulmonary function of patients with COPD.It was compare with that control group before treatment of treatment group,and the lung function(FEV1)was comparable,but there was no statistical difference.After2 months of treatment,the treatment group and control group in FEV1 levels are higher than before the treatment,the treatment group compared with control group no significant difference.2.LWBQ capsule can improve clinical symptoms and syndrome differentiation of TCM.Compared with the control group before treatment,TCM syndrome score was comparable,but there was no statistical difference.Before treatment,the treatment group compared with the control group,the TCM syndrome score was comparable,but there was no statistical difference.After 2 months of treatment,the treatment group of TCM clinical syndrome score was significantly decreased,the control group of TCM clinical syndrome integral was reduced,the treatment group than the control group of TCM clinical syndrome integral decline is more apparent.Conclusion:1.LWBQ capsule can relieve the lung function and histopathological inflammation in the COPD model,and inhibit the release of inflammatory cytokines;2.LWBQ capsule may inhibit the phosphorylation level of the JAKs/STATs signaling pathway and thus achieve the therapeutic effect of the rat model of chronic obstructive pulmonary disease;3.LWBQ capsule can stabilize the pulmonary function of patients with COPD and improve the clinical symptoms of patients and TCM syndrome integration. |
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