Bufei Yishen granules suppress oxidative stress in rats with chronic obstructive pulmonary disease via Nrf2 signaling

OBJECTIVE To explore the antioxidant effect of Bufei Yishen granules on chronic obstructive pulmo⁃nary disease(COPD)and investigate its underlying mechanism.METHODS Forty-eight rats were randomly divided into normal,model,Bufei Yishen granules(BY)and N-acetylcysteine(NAC)groups,12 rats in each group.The stable COPD rat model was duplicated by using repeated cigarette smoke exposure combined with Klebsiella bacterial infection for 12 weeks(week 1-12),and the corresponding drugs were administered for the next 8 weeks(week 13-20).Minute volume(MV),tidal volume(TV)and peak expiratory flow(PEF)were measured by whole body plethysmography(WBP)system every 4 weeks.Before sacrificed,forced vital capacity(FVC)and forced expiratory volume 0.1(FEV0.1)were measured byPFT system.The pathological changes of lung tissue were observed by pathological techniques.Heme oxygenase 1(HO-1),superoxide dismutase 1(SOD1)and Nrf2 in lung tissue were measured by immunohisto-hemical method.The total anti oxidizing capability(T-AOC),lipid peroxide(LPO)in rat serum were measured.The expression of Nrf2,HO-1 andγ-glutamyl cysteine synthetase(γ-GCS)mRNA in lung tissue was detected by quantitative polymerase chain reac⁃tion(qPCR).The protein expression of Keap1,Nrf2 and HO-1 in lung tissue were detected by Western blotting.RESULTS①Lung function:compared with normal group,the MV in model group was significantly decreased at week 8(P<0.01),the TV and PEF were significantly decreased at week 4(P<0.01).At week 20,compared with model group,MV,TV,and PEF in the BY and NAC groups were significantly increased(P<0.01);compared with the NAC group,MV,TV,and PEF in BY group were significantly increased(P<0.01).At the end of week 20,the FVC and FEV0.1 in model group were significantly lower than that in normal group(P<0.01).Compared with model group,the FVC and FEV0.1 in the BY and NAC groups were significantly increased(P<0.05).②Oxidative indexes:Compared with Normal group,T-AOCin serum was significantly decreased in Model group,while LPO was significantly increased(P<0.01).Compared with the Model,T-AOC in BY and NAC groups was significantly increased(P<0.01),and the LPO was significantly decreased(P<0.05,P<0.01).There were no difference between the BTG and NAC.③Nrf2 signaling:Nrf2 and HO-1 in lung tissue were mainly expressed in the cytoplasm and part of the nucleus of alveolar epithelial cells.SOD1 protein was mainly distributed in bronchial epithelial cells and alveolar septa.Compared with normal group,the expression of Nrf2 in the model group was increased(P<0.01),and HO-1 and SOD1 were decreased(P<0.01).Compared with the model,the expression of Nrf2 in the BY group was significantly increased(P<0.05),and HO-1 and SOD1 in BY and NAC groups were both increased(P<0.01).Compared with the NAC group,the expression of HO-1 in BY group was increased(P<0.01).Compared with normal group,the Nrf2 mRNA expression of lung tissue in the model was significantly increased(P<0.01),the HO-1 andγ-GCS mRNA was decreased(P<0.01).Compared with model group,the Nrf2,HO-1,andγ-GCS mRNA in the BY group were increased(P<0.01),the HO-1,andγ-GCS mRNA in NAC group were increased(P<0.01).Compared with normal group,the Nrf2 protein expression of lung tissue in the model group was significantly increased(P<0.01),and HO-1 protein expression was significantly decreased(P<0.01).Compared with the model,the Nrf2 and HO-1 protein in NAC and BY groups was significantly increased(P<0.01).CONCLUSION Bufei Yishen gran⁃ules has beneficial curative effect in COPD rats,and has the same antioxidation effect as NAC,the mechanism may be involved in upregulating Nrf2 signaling.