海南医科大学学报2025，Vol.31Issue(18)：1418-1426,9.DOI:10.13210/j.cnki.jhmu.20241121.002
BMSCs通过miR-132-3p调控巨噬细胞M2型极化减轻脓毒症诱导的急性肺损伤
BMSCs reduce sepsis-induced acute lung injury by regulating macrophage M2 polarization through miR-132-3p
摘要
Abstract
Objective:To explore the regulatory effects of bone marrow mesenchymal stem cells(BMSCs)through miR-132-3p affecting the polarization of macrophages towards the M2 type,thereby revealing and verifying the potential mecha-nism of this process in alleviating sepsis-induced acute lung injury.Methods:MiR-132-3p mimics were transfected into BMSCs us-ing Lipofectamine™ 2000.A septic lung injury model was induced via cecal ligation and puncture,followed by the assessment of the MSS score.qRT-PCR was employed to measure the expression levels of miR-132-3p in lung tissue.H&E staining was per-formed to observe the pathological changes in lung tissue across the different experimental groups.ELISA was utilized to quantify the serum levels of TNFα,IL-1β,and IL-6.Western blot analysis was conducted to evaluate the expression levels of inducible ni-tric oxide synthase(iNOS),TNF-α,IL-1β,Arg1,and CD206 in macrophages isolated from bronchoalveolar lavage fluid.In cell experiments,RAW264.7 cells were induced with 100 ng/mL lipopolysaccharide(LPS),and miR-132-3p mimics were transfect-ed into BMSCs,which were then co-cultured with RAW264.7 cells.A dual-luciferase reporter assay confirmed TRIB1 as the tar-get gene of miR-132-3p.Western blot analysis was performed again to assess the expression levels of TNF-α,IL-1β,Arg1,CD206,TRIB1,and p-NF-κB p65 in RAW264.7 cells.Results:In animal experiments,the Model group exhibited an increase in the MSS score compared to the Sham group,alongside severe lung tissue damage.Additionally,the expression of miR-132-3p de-creased,while serum inflammatory factors such as TNFα,IL-1β,and IL-6 significantly increased.Alveolar macrophages showed elevated levels of iNOS,TNF-α,and IL-1β,whereas Arg1 and CD206 levels decreased in these cells.In contrast,the BMSCs group demonstrated a reduction in the MSS score,improved lung tissue damage,and an increase in miR-132-3p expression com-pared to the Model group.Serum inflammatory factors TNFα,IL-1β,and IL-6 significantly decreased,along with reductions in iNOS,TNF-α,and IL-1β,while Arg1 and CD206 levels increased.Furthermore,the BMSCs-miR-132-3p-OE group was found to enhance these changes in mice.In cell experiments,dual-luciferase assays indicated that miR-132-3p can target TRIB1.Com-pared to the LPS group,the LPS-BMSCs-miR-132-3p-OE group exhibited decreased levels of TNF-α,IL-1β,and p-NF-κB p65,while levels of miR-132-3p,Arg1,CD206,and TRIB1 were increased.Conclusion:BMSCs can mitigate sepsis-induced acute lung injury by regulating macrophage M2 polarization via miR-132-3p.关键词
急性肺损伤/骨髓间充质干细胞/巨噬细胞极化/miR-132-3pKey words
Acute lung injury/Bone marrow mesenchymal stem cells/Macrophage polarization/miR-132-3p分类
医药卫生引用本文复制引用
邓乐秀,王苑娣,常建亮,李琛,朱梓嫣,刘建华,彭晓翠,张志华..BMSCs通过miR-132-3p调控巨噬细胞M2型极化减轻脓毒症诱导的急性肺损伤[J].海南医科大学学报,2025,31(18):1418-1426,9.基金项目
This study was supported by the Natural Science Foundation of Hebei Province(H2023405053) 河北省自然科学基金资助项目(H2023405053) （H2023405053）
