中国临床药理学杂志2025，Vol.41Issue(23)：3335-3342,8.DOI:10.13699/j.cnki.1001-6821.2025.23.006
苹果多酚调节miR-21-5p/SKP2通路对慢性阻塞性肺疾病急性加重期大鼠肺功能及免疫失衡的影响
The effects of apple polyphenols on lung function and immune imbalance in rats with acute exacerbation of chronic obstructive pulmonary disease by adjusting the miR-21-5p/SKP2 pathway
摘要
Abstract
Objective To explore the effects of apple polyphenols(AP)on lung function and immune imbalance in rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)by adjusting the miR-21-5p/SKP2 pathway.Methods The stable stage of COPD was established by cigarette smoking and endotoxin infusion,and then AECOPD rats were established by nasal infusion of Staphylococcus aureus bacterial solution.They were randomly assigned into the AECOPD group,the AP-25 group,the AP-100 group,the dexamethasone group,the AP-100+NC agomir group,and the AP-100+miR-21-5p agomir group.And rats intervened with normal saline were as the control group.Subsequently,tracheal intubation was performed to measure the peak expiratory and inspiratory flow rates(PEF,PIF),and the ratio of forced expiratory volume to forced vital capacity in 0.3 seconds(FEV0.3/FVC).Serum was collected to measure the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Bronchoalveolar lavage fluid(BALF)was recovered,and the numbers of neutrophils,lymphocytes and macrophages were determined.Left lung lobe sections were prepared,and lung tissue lesions and scores were observed.The right lung tissue of rats was taken.The proportions of Th 17 and Treg cells,the mRNA expression of miR-21-5p and SKP2,and the protein expression of retinoic acid-related orphan receptor γt(RORγt),IL-17A,forkhead box protein P3(Foxp3),IL-10 and SKP2 in the lung tissue were detected.Results The AECOPD group had higher RORγt,IL-17A,miR-21-5p,TNF-α,IL-6,macrophages,neutrophils,lymphocytes,Th17 cell proportion,and Th17/Treg than the control group,and had lower Foxp3,IL-10,SKP2 mRNA and protein expression,Treg cell proportion,PEF,PIF,and FEV0.3/FVC than the control group(P＜0.05).The AP-25 group,AP-100 group and dexamethasone group had lower RORγt,IL-17A,miR-21-5p,TNF-α,IL-6,macrophages,neutrophils,lymphocytes,Th17 cell proportion,and Th17/Treg than the AECOPD group,and had higher Foxp3,IL-10,SKP2 mRNA and protein expression,Treg cell proportion,PEF,PIF,and FEV0.3/FVC than the AECOPD group(P＜0.05).In addition,miR-21-5p agomir reversed the protective effect of AP on AECOPD rats.Conclusion AP improves lung function and immune imbalance in AECOPD rats by inhibiting the miR-21-5p/SKP2 pathway.关键词
苹果多酚/慢性阻塞性肺疾病急性加重期/肺功能/免疫失衡Key words
apple polypheno/acute exacerbation of chronic obstructive pulmonary disease/lung function/immune imbalance分类
医药卫生引用本文复制引用
冯平,姬泽萱,宋凯艳,陈丽萍,王布,钱海红,张志华..苹果多酚调节miR-21-5p/SKP2通路对慢性阻塞性肺疾病急性加重期大鼠肺功能及免疫失衡的影响[J].中国临床药理学杂志,2025,41(23):3335-3342,8.基金项目
2020年度河北省医学科学研究课题(20200534) （20200534）
张家口市2023年市级科技计划自筹经费项目(2322090D) （2322090D）
