Atorvastatin calcium promotes the recovery of lung tissue injury in rats with chronic obstructive pulmonary disease by up-regulating the SIRT1/NF-κB signaling pathway

LI Wei; AN Xing; LIU Lei

doi:10.13431/j.cnki.immunol.j.20240115

Abstract：Objective To investigate the effect of atorvastatin calcium(ATR)on lung tissue injury in rats with chronic obstructive pulmonary disease(COPD)by regulating the sirtuin type 1(SIRT1)/NF-κB signaling pathway.Methods COPD rats were established by tracheal injection of lipopolysaccharide combined with smoking,and rats injected with physiological saline alone were used as the control group.COPD rats were randomly assigned into COPD group,ATR(5 mg/kg)group,positive drug(0.2 mg/kg dexamethasone)group,inhibitor(5 mg/kg EX527)group,and ATR+inhibitor group.After the intervention,the forced expiratory volume in the first second/forced vital capacity(FEV1/FVC)and peak expiratory flow(PEF)of the rats were measured.Blood samples were collected from the abdominal aorta,and the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β in the supernatant were detected;the lung tissue was isolated,and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA),and pathological changes were detected and the degree of tissue damage were scored.Meanwhile,the expression of SIRT1 and NF-κB p65 mRNA and protein were detected.Results The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the COPD group were higher than those in the control group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein were lower than those in the control group(P<0.05).The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the ATR group and positive drug group were lower than those in the COPD group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein were higher than those in the COPD group(P<0.05).The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the inhibitor group were higher than those in the COPD group,however,the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein were lower than those in the COPD group(P<0.05).The levels of TNF-α,IL-1β,IL-6,MDA,pathological score,and the expression of NF-κB p65 mRNA,and p-NF-κB p65/NF-κB p65 in the ATR+EX527 group were higher than those in the ATR group,but lower than those in the EX527 group(P<0.05),while the FEV1/FVC,PEF,level of SOD,and the expression of SIRT1 mRNA and protein in the ATR+inhibitor group were lower than those in the ATR group,but higher than those in the inhibitor group(P<0.05).Conclusion ATR alleviate the lung tissue damage in COPD rats by upregulating SIRT1 expression and inhibiting NF-κB expression.