人脐带间充质干细胞外泌体对大鼠慢性阻塞性肺疾病的影响OA

Objective To investigate the therapeutic effect of human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC EXO)on rats with chronic obstructive pulmonary disease(COPD).Methods Fifty Sprague-Dawley(SD)rats were randomly divided into five groups(n=10 per group):Control(healthy rats),COPD(COPD rats),Aminophylline(rats with COPD treated with 2.3 mg/kg amino-phylline through gavage),EXO(rats with COPD administered hUC-MSC EXO through tail vein injection),and FPS-ZM1[rats with COPD administered the receptor for advanced glycation end products(RAGE)inhibitor FPS-ZM1 through tail vein injection].After modeling and drug administration,pulmonary function was assessed,inflammatory cell counts and cytokine levels in bronchoalveolar lavage fluid were measured,and the wet-to-dry weight(W/D)ratio of lung tissues was calculated.Pathological changes in lung tissues were analyzed using hematoxylin and eosin staining.Reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)levels in lung tissues were measured.RAGE,phosphorylated phosphatidylinositol 3-kinase(p-PI3K),and phosphorylated protein kinase B(p-AKT)protein expressions were determined using Western blotting.Results Compared with the Control group,the COPD group showed a significantly decreased forced expiratory volume in one second/forced vital capacity(FEV1/FVC),peak expiratory flow(PEF),and SOD and GSH levels(P<0.05),whereas the W/D ratio;lymphocyte,macrophage,and white blood cell counts;IL-6,IL-1β,and TNF-α levels;ROS and MDA level;RAGE protein expression,p-PI3K/PI3K,and p-AKT/AKT were significantly increased(P<0.05).Compared with the COPD group,the Aminophylline,EXO,and FPS-ZM1 groups exhibited significantly increased FEV1/FVC,PEF,and SOD and GSH levels(P<0.05),as well as significantly decreased W/D ratio;inflammatory cell counts;cytokine levels;oxidative stress marker levels;and RAGE protein expression,p-PI3K/PI3K,and p-AKT/AKT(P<0.05).Compared with the Aminophylline group,the EXO group showed further improvements in lung function parameters and antioxidant levels,as well as reductions in inflammatory markers,oxidative stress markers,and RAGE protein expression,p-PI3K/PI3K,and p-AKT/AKT(P<0.05).Conversely,the FPS-ZM1 group showed worsened lung function;reduced antioxidant capacity;and increased inflammation,oxidative stress,and RAGE protein expression,p-PI3K/PI3K,and p-AKT/AKT compared with the EXO group(P<0.05).Conclusion hUC-MSC EXO can significantly alleviate oxidative stress and inflammation,thereby ameliorating COPD progression in rats,potentially through inhibition of the RAGE/ROS signaling pathway.