沙参麦冬汤通过抑制cGAS-STING-NF-κB介导的炎性衰老改善老年COPD小鼠肺功能OA

Objective To investigate the effect of Shashen Maidong Decoction(SMD)on inflammaging in a mouse model of chronic obstructive pulmonary disease(COPD),and to determine whether its efficacy is mediated by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)-nuclear factor-kappa B(NF-κB)signaling pathway.Methods Female and male C57BL/6JNifdc mice(half male and half female)aged 18-20 months were selected to establish a COPD model was subsequently established via cigarette smoke exposure combined with intranasal lipopolysaccharide instillation.The mice were randomly assigned to 6 groups,including a normal control group,a model group,low-,medium-,and high-dose SMD groups(receiving 8.3,16.5,and 33.0 g/kg,respectively),and a dexamethasone group(3 mg/kg),with 8 mice in each group(4 males and 4 females).Starting on the day after modelling,the mice received daily intragastric administration for 12 weeks(normal control and model groups received sodium carboxymethyl cellulose at 0.15 mL/10 g).Pulmonary function parameters,including resistance of the respiratory system(Rrs),elastance of the respiratory system(Ers),the ratio of forced expiratory volume in 0.2 seconds to forced vital capacity(FEV0.2/FVC),and forced expiratory flow at 50%of vital capacity(FEF50%),were measured.Lung histopathology was evaluated by hematoxylin and eosin(HE)and Masson's trichrome stains.Serum inflammatory factors,including interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and tumor necrosis factor α(TNF-α),as well as oxidative stress markers,including superoxide dismutase(SOD)and malondialdehyde(MDA),were assessed.In addition,the mRNA and protein expression levels of senescence-associated proteins(p16 and p21)and the cGAS-STING-NF-κB pathway molecules in lung tissues were determined.Results Compared with the normal control group,mice in the model group exhibited impaired pulmonary function,characterized by increased Rrs and decreased Ers,FEV0.2/FVC,and FEF50%.Histopathologic examination demonstrated massive inflammatory cell infiltration,bronchiolar wall thickening,and destruction of alveolar structures.The levels of serum inflammatory factors and MDA were increased,whereas SOD activity was decreased,demonstrating statistically significant differences(all P<0.01).Furthermore,the mRNA and protein expression levels of senescence-associated proteins and cGAS-STING-NF-κB pathway molecules were significantly elevated in lung tissues(all P<0.01).Compared with the model group,the medium-and high-dose SMD groups showed significantly improved lung function parameters,decreased serum inflammatory factors and MDA levels,and increased SOD activity(all P<0.05).In addition,the expression levels of senescence-associated proteins and cGAS-STING-NF-κB pathway molecules in lung tissues were significantly downregulated(all P<0.05).Conclusion SMD ameliorates lung function impairment,particularly FEV0.2/FVC,in COPD mice.The underlying mechanism may have involved the inhibition of inflammaging mediated by the cGAS-STING-NF-κB signaling pathway.SMD can protect against lung function impairment,particularly centered on FEV0.2/FVC,in COPD mice.The potential mechanism may involve the inhibition of inflammaging mediated by the cGAS-STING-NF-κB signaling pathway.