骨髓间充质干细胞来源外泌体对慢性阻塞性肺疾病大鼠肺功能及SIRT1/NF-κB信号通路的影响OA

Objective To investigate the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSCs-EXO)on pulmonary function and the silent information regulator 1(SIRT1)/nuclear factor-κB(NF-κB)signaling pathway in rats with chronic obstructive pulmonary disease(COPD).Methods A rat model of COPD was established by combined lipopolysaccharide and cigarette smoke exposure.Rats were divided into a control group,a COPD group,a COPD+EXO group and a COPD+EXO+EX527 group(EX527 is a SIRT1 inhibitor),with 8 rats in each group.BMSCs-EXO were administered via aerosol inhalation.Pulmonary func-tion parameters of rats in each group were measured using a small animal pulmonary function testing system.Histopathological injury of lung tissue was evaluated by HE staining,and pulmonary fibrosis was assessed by Masson staining.Serum levels of interleukin(IL)-6,IL-8 and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay.The protein expressions of SIRT1 and nuclear factor-κB inhibitor alpha(IκBα),as well as the ratio of phosphorylated(p)-NF-κB p65 to NF-κB p65 in rat lung tissue,were determined by Western blotting.Results Compared with the control group,pulmonary function parameters in the COPD group were significantly decreased(P<0.05),obvious pathological injury of lung tissue was observed,the percentage of collagen fiber area in lung tissue was significantly increased(P<0.05),serum levels of IL-6,IL-8 and TNF-α were significantly elevated(P<0.05),the protein expression levels of SIRT1 and IκBα in lung tissue were significantly decreased(P<0.05),and the ratio of p-NF-κB p65 to NF-κB p65 was significantly increased(P<0.05).Compared with the COPD group,pulmonary function parameters in the COPD+EXO group were significantly increased(P<0.05),pathological injury of lung tissue was alleviated,the percentage of collagen fiber area in lung tissue was significantly decreased(P<0.05),serum levels of IL-6,IL-8 and TNF-α were significantly decreased(P<0.05),the protein expression levels of SIRT1 and IκBα in lung tissue were significantly increased(P<0.05),and the ratio of p-NF-κB p65 to NF-κB p65 was significantly de-creased(P<0.05).Compared with the COPD+EXO group,pulmonary function parameters in the COPD+EXO+EX527 group were significantly decreased(P<0.05),pathological injury of lung tissue was exacerba-ted,the percentage of collagen fiber area in lung tissue was significantly increased(P<0.05),serum levels of IL-6,IL-8 and TNF-α were significantly elevated(P<0.05),the protein expression levels of SIRT1 and IκBα in lung tissue were significantly decreased(P<0.05),and the ratio of p-NF-κB p65 to NF-κB p65 was signifi-cantly increased(P<0.05).Conclusion BMSCs-EXO may improve pulmonary function in rats with COPD by inhibiting inflammation through the regulation of the SIRT1/NF-κB signaling pathway.