调补肺肾三法通过抑制ERK1/2信号通路改善COPD大鼠气道黏液高分泌OA北大核心CSTPCD

Objective To investigate the roles of three Tiao-Bu Fei-Shen Traditional Chinese Medicine(TCM)therapies in improving airway mucus hypersecretion in rats with stable chronic obstructive pulmonary disease(COPD).Methods Ninety rats were divided randomly into nine groups:control(Control)group,model(COPD)group,Bu-Fei Jian-Pi Formula(BJF)group,Bu-Fei Yi-Shen Formula(BYF)group,Yi-Qi Zi-Shen Formula(YZF)group,ERK1/2 inhibitor(PD98059)group,Bu-Fei Jian-Pi combined with inhibitor(BJF+PD98059)group,Bu-Fei Yi-Shen combined with inhibitor(BYF+PD98059)group,and Yi-Qi Zi-Shen combined with inhibitor(YZF+PD98059)group.A rat model of COPD was established by exposing rats to cigarette smoke followed by repeated bacterial infection from weeks 1～8.From weeks 9～16,rats in the control and COPD groups were given 2 mL normal saline,rats in the BJF,BYF,and YZF groups were given the three Tiao-Bu Fei-Shen formulas by gavage,and rats in the PD98059,BJF+PD98059,BYF+PD98059,and YZF+PD98059 groups were given PD98059 by intraperitoneal injection for 7 days at the 16th week.Lung function tests were conducted after 16 weeks and lung tissue morphology,lung water content,inflammatory cell count in bronchoalveolar lavage fluid,and serum levels of inflammatory factors were also assessed.Goblet cell proportion was determined by Alcian blue-periodic acid-Schiff staining,and Muc5AC and Muc5B expression levels were detected by immunohistochemistry.mRNA expression levels of ERK1,ERK2,ENaC,CFTR,and AQP5 were detected by polymerase chain reaction and protein expression levels of ERK1/2 and P-ERK1/2 in lung tissue were determined by Western Blot.Results TV,MV,FVC,FEV0.1,FEV0.1/FVC were significantly decreased(P＜0.01)in COPD rats compared with those in the control group.Lung pathology revealed alveolar disorder,massive fracture of the alveolar wall,and severe shrinkage/thickening of the airway wall accompanied by extensive infiltration of inflammatory cells.Lung tissue water content was significantly increased in COPD rats(P＜0.01),while the proportion of macrophages in BALF was significantly reduced(P＜0.01)and the proportions of neutrophils and lymphocytes were significantly increased(P＜0.01).Serum levels of TNF-α and IL-1β were significantly increased in COPD rats(P＜0.05,P＜0.01).The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells were significantly increased(P＜0.01),mRNA expression levels of ERK1,ERK2,and ENaC in lung tissue were significantly elevated(P＜0.01),while mRNA expression levels of CFTR and AQP5 were significantly decreased(P＜0.01)in COPD rats compared with levels in the control group.The expression of P-ERK1/2,ERK1/2 in lung tissue was significantly increased(P＜0.01)Rats in the treatment groups demonstrated improvements in the above indicators(P＜0.05,P＜0.01)compared with the COPD group,the groups receiving the three Tiao-Bu Fei-Shen formulas combined with PD98059 showing superior efficacy compared with the single treatment groups(P＜0.05,P＜0.01).Conclusions The three tested Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1/2 signaling pathway.