Study on the Effect and Mechanism of Guizhi Fuling Pill(桂枝茯丸)on Improving Airway Remodeling in COPD Mice Based on MEK/ERK Pathway
Objective To study on the effect and mechanism of Guizhi Fuling pill on improving airway remodeling in chronic obstructive pulmonary disease(COPD)mice through the MEK/ERK pathway.Methods:A COPD mouse model was established using smoking method.Totally 32 COPD model mice were randomly divided into model group,Guizhi Fuling pill group,PD98059 group and Guizhi Fuling pill+PD98059 group,with 8 mice in each group.Another 8 mice were selected as the blank group.Corresponding drugs were administered orally for 14 days.Small animal lung function analyzer was used to measure minute ventilation volume(MV),peak expiratory flow(PEF)and peak inspiratory flow(PIF)in mice.HE staining was used to evaluate lung tissue inflammation.Masson staining was used to observe airway remodeling changes,and Western blotting was used to detect the relative expression levels of COL1A1,COL3A1,MEK1,p-MEK1,ERK(1/2)and p-ERK(1/2)proteins.Results:The model group showed lower levels of MV,PIF and PEF than blank group(P＜0.05).Compared with the blank group,there were significant inflammation and airway remodeling in lung tissue in model group.The model group showed higher levels of COL1A1,COL3A1,p-MEK1,p-ERK(1/2),p-MEK/MEK and p-ERK(1/2)/ERK(1/2)than blank group(P＜0.05).Guizhi Fuling pill group,PD98059 group,and Guizhi Fuling pill+PD98059 group showed higher level of MV,PEF and PIF than model group(P＜0.05),while lower levels of COL1A1,COL3A1,p-MEK1,p-ERK(1/2),p-MEK/MEK and p-ERK(1/2)/ERK(1/2)in lung tissue than model group(P＜0.05).Compared with model group,lung tissue inflammation and airway remodeling were improved in Guizhi Fuling pill group,PD98059 group and Guizhi Fuling pill+PD98059 group.Guizhi Fuling pill+PD98059 group showed higher levels of MV,PIF and PEF than Guizhi Fuling pill group and PD98059 group(P＜0.05),and there was no statistically significant difference in the levels of MV,PIF and PEF between Guizhi Fuling pill group and PD98059 group(P＞0.05).Guizhi Fuling pill group showed lower relative expression levels of COL1A1 and COL3A1 proteins than PD98059 group(P＜0.05),while higher relative expression levels of COL1A1 and COL3A1 proteins than Guizhi Fuling pill+PD98059 group(P＜0.05).PD98059 group showed higher relative expression levels of COL1A1 and COL3A1 proteins than Guizhi Fuling pill+PD98059 group(P＜0.05).Guizhi Fuling pill group showed lower p-MEK1,p-ERK(1/2),p-MEK1/MEK1 and p-ERK(1/2)/ERK(1/2)than PD98059 group(P＜0.05),while higher p-MEK1,p-ERK(1/2),p-MEK1/MEK1 and p-ERK(1/2)/ERK(1/2)than Guizhi Fuling pill+PD98059 group(P＜0.05).The PD98059 group showed higher p-MEK1,p-ERK(1/2),p-MEK1/MEK1 and p-ERK(1/2)/ERK(1/2)than Guizhi Fuling pill+PD98059 group(P＜0.05).Conclusion:Guizhi Fuling pill can significantly improve the airway remodeling process in COPD mice,and inhibiting the MEK/ERK pathway may be one of its mechanisms of action.
万方数据
维普
