四川大学学报（医学版）2026，Vol.57Issue(4)：974-984,11.DOI:10.12182/20260760107
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
Shashen Maidong Decoction Improves Pulmonary Function in Aged Mice With Chronic Obstructive Pulmonary Disease by Inhibiting cGAS-STING-NF-κB-Mediated Inflammaging
摘要
Abstract
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.关键词
肺疾病,慢性阻塞性/沙参麦冬汤/衰老/炎症/NF-κBKey words
Pulmonary disease,chronic obstructive/Shashen Maidong Decoction/Aging/Inflammation/Nuclear factor-kappa B引用本文复制引用
旷湘楠,刘星冉,赵欣瑶,陈雪晓,刘时乔..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[J].四川大学学报（医学版）,2026,57(4):974-984,11.基金项目
This study was supported by National Natural Science Foundation of China(No.82405276),Scientific Research Program Project of the Hebei Administration of Traditional Chinese Medicine(No.2023116),and Hebei Higher Education Institutions Scientific and Technological Research Project(No.BJK2024112). 国家自然科学基金青年科学基金项目(No.82405276)、河北省中医药管理局科研计划项目(No.2023116)和河北省高等学校科研技术研究项目(No.BJK2024112)资助 （No.82405276）
