The Effect Of Qizhi Zhoufei Granules On Expression Of KLF2,Nrf2 And γ-GCS In Lung Tissue Of COPD Rats

Objective To observe the effect of Qizhi zhoufei granules on the expression of Krüppel-like factor 2(KLF2),Nuclear factor erythroid-2-related factor 2(Nrf2)and gama-Glutamylcysteine synthetase(gama-GCS)in lung tissue of rats with chronic obstructive pulmonary disease(COPD),to analyze the antioxidant mechanism of Qizhi Zhoufei granules under oxidative stress of COPD,and to provide a new theoretical basis for the pathogenesis and treatment of COPD.Methods 60 SPF grade Wistar male rats were randomly divided into 10 groups as the control group,and the remaining 50 were used as model rats.The COPD rats model was duplicated by intratracheal injection of lipopolysaccharide combined with smoking.At the end of the 28 th day,the remaining rats were randomly divided into the model group,positive control group,and high,middle and low dose groups of Qizhi Zhoufei granules.The drug intervention began on the 29 th day,the control group and the model group were given the same volume of normal saline as the medication group;the positive control group was given dexamethasone acetate solution;the high,middle and low dose groups of the Qizhi Zhoufei granules were given different concentrations of Qizhi Zhoufei granules solution respectively.After 28 days of drug intervention,the changes of pulmonary function in anesthetized rats were detected,and the lung tissue samples were collected after cervical dislocation death.The expression of KLF2,Nrf2 and gama-GCS m RNA in lung tissue was detected by Q-PCR,the expression of KLF2,Nrf2 and gama-GCS protein in lung tissue was detected by Western Blot,and the expression of KLF2,Nrf2 protein in lung tissue was detected by immunohistochemical.Results1.General state observation of ratsCompared with the control group,the model group had dim hair color,poor mental state,less lying and less movement,hysteria,slow reaction,shortness of breath,increase of airway secretion and decrease of body weight.Compared with the model group,the hair color,respiration,mental state and body weight of the rats in the positive control group and Qizhi Zhoufei high,medium and low dose groups were improved in different degrees,and the Qizhi Zhoufei groups was superior to the positive control group.2.Changes of pulmonary function in ratsCompared with the control group,the PIF,PEF,EF50,TV,EV and Cdyn of the model group were decreased(P<0.05);the F was increased(P<0.05).Compared with the model group,PIF,PEF,EF50,TV and Cdyn were increased in the positive control group and Qizhi Zhoufei high,medium and low dose groups(P<0.05).The EV was increased in the positive control group and the Qizhi Zhoufei high and medium dose groups(P<0.05).F was decreased in the Qizhi Zhoufei high and medium dose groups(P<0.05).3.Changes of KLF2,Nrf2 and gama-GCS m RNA expression in rat lung tissueCompared with the control group,the expression level of KLF2,Nrf2 and gama-GCS m RNA in the model group were increased(P<0.05).Compared with the model group,the expression level of KLF2 and Nrf2 m RNA in the positive control group,the high,middle and low dose groups of the Qizhi Zhoufei were decreased(P<0.05);the expression level of gama-GCS m RNA in the high,middle and low dose groups of the Qizhi Zhoufei were decreased(P<0.05).4.Changes of KLF2,Nrf2 and gama-GCS protein expression in rat lung tissueThe results of Western Blot showed that compared with the control group,the expression level of KLF2,Nrf2 and gama-GCS protein in the model group were increased(P<0.05).Compared with the model group,the expressions level of KLF2 and Nrf2 in the positive control group,the high,middle and low doses of the Qizhi Zhoufei were decreased(P<0.05);the expression level of gama-GCS the high,middle and low doses of the Qizhi Zhoufei were decreased(P<0.05).The results of immunohistochemical showed that compared with the control group,the expression level of KLF2 and Nrf2 protein in the model group were increased(P<0.05).Compared with the model group,the expression level of KLF2 and Nrf2 protein in the positive control group and the high,middle and low doses of the Qizhi Zhoufei were decreased(P<0.05).Conclusions1.Qizhi Zhoufei granules can improve the general condition and lung function of COPD rats,slow down the oxidative stress and improve the antioxidant capacity.2.Qizhi Zhoufei granules has antioxidant effect on COPD.The mechanism may activate the expression KLF2,Nrf2 to promote the activate of gama-GCS,and increase the antioxidant substances in vivo to regulate the oxidation/antioxidation imbalance,thereby slowing the occurrence,development and deterioration of COPD.