脂肪来源间充质干细胞通过抑制巨噬细胞焦亡减轻辐射诱导的急性肺损伤的机制探究
Adipose-Derived Mesenchymal Stem Cells Alleviate Radiation-Incuced Acute Lung Injury through Inhibtion of Macrophage Pyroptosis: A Mechanistic Insight
路景帆 1蒋杏宁 1胡耀文 1刘延豪 1刘妍妍 1谭慧玲 1杨巍1
作者信息
- 1. 苏州大学放射医学与防护学院，苏州 215123
- 折叠
摘要
目的：本研究旨在探讨脂肪来源间充质干细胞（ADSCs）改善辐射诱导急性肺损伤的治疗作用，揭示ADSCs通过抑制巨噬细胞焦亡介导的抗炎机制。方法:从C57BL/6腹股沟双侧脂肪提取脂肪来源间充质干细胞，通过流式细胞术检测间充质干细胞表面标志物；通过成骨成脂分化实验检测分化能力；通过酶联免疫吸附实验（ELISA）实验测定干细胞抗炎因子释放能力。提取C57BL/6骨髓细胞分化培养小鼠骨髓来源巨噬细胞(BMDM)，辐照后与脂肪来源间充质干细胞共培养，流式细胞术检测巨噬细胞（BMDM）焦亡情况,酶联免疫吸附实验检测巨噬细胞焦亡炎症因子释放情况。构建C57BL/6小鼠放射性肺损伤模型，尾静脉分别给予PBS、1×10的4次方、1×10的5次方、1×10的6次方细胞数量脂肪来源间充质干细胞（ADSC），取照射后60天的小鼠肺组织，通过HE染色、PCR等方法等方法检测电离辐射后小鼠肺组织损伤的情况。结果：提取高纯度的具有成骨成脂分化能力（茜素红和油红O染色）的脂肪来源间充质干细胞，ADSCs 在连续培养体系中具备持续分泌IL-1RA、TNFAIP6、IL-10抗炎因子能力。脂肪来源间充质干细胞共培养减轻了辐照后小鼠骨髓来源巨噬细胞的Caspase1和PI双阳性细胞的比例和炎症因子IL-1β、TNF-α和细胞毒性标志物LDH的释放。HE染色证明随着注射ADSCs细胞数量的增加，减轻了辐射诱导的小鼠放射性肺损伤程度，减轻了肺部炎症因子TNF-α、 IL-6、IL-1βmRNA的表达。结论: 间充质干细胞（MSCs）治疗可有效减轻辐射诱导的肺损伤，下调肺部炎症因子水平。其潜在机制可能是通过抑制巨噬细胞焦亡，从而阻断由焦亡驱动的炎症级联反应。
Abstract
Objective: To investigate the therapeutic effects of adipose-derived mesenchymal stem cells (ADSCs) on radiation-induced acute lung injury and elucidate their anti-inflammatory mechanisms via inhibiting macrophage pyroptosis.
Methods: C57BL/6 mouse-derived ADSCs were isolated, characteAdipose-Derived Mesenchymal Stem Cells Alleviate Radiation-Incuced Acute Lung Injury through Inhibtion of Macrophage Pyroptosis: A Mechanistic Insightrized (flow cytometry, differentiation assays), and their anti-inflammatory cytokine release was quantified (ELISA). Irradiated bone marrow-derived macrophages (BMDMs)were co-cultured with ADSCs to assess pyroptosis and inflammatory factor release.A mouse model of radiation-induced lung injury was established and treated intravenously with varying doses of ADSCs (1×10? to 1×10? cells). Lung damage and inflammation were evaluated 60 days post-irradiation via H&E staining and PCR.Results: Cultured ADSCs sustainably secreted anti-inflammatory factors (IL-1RA, TNFAIP6, IL-10). Co-culturing irradiated BMDMs with ADSCs significantly reduced Caspase-1/PI double-positive cells, inflammatory cytokines (IL-1β, TNF-α), and LDH release. In vivo, ADSC treatment dose-dependently mitigated radiation-induced lung damage and downregulated pulmonary TNF-α, IL-6, and IL-1β mRNA expression.Conclusion: ADSC therapy effectively attenuates radiation-induced lung injury and inflammation by inhibiting macrophage pyroptosis, thereby blocking the pyroptosis-driven inflammatory cascade.关键词
急性放射性肺损伤/间充质干细胞/焦亡/炎症小体/巨噬细胞Key words
Acute radiation-induced lung injury/Mesenchymal stem cells/Pyroptosis/Inflammasome/Macrophage引用本文复制引用
路景帆,蒋杏宁,胡耀文,刘延豪,刘妍妍,谭慧玲,杨巍.脂肪来源间充质干细胞通过抑制巨噬细胞焦亡减轻辐射诱导的急性肺损伤的机制探究[EB/OL].(2026-05-25)[2026-05-26].http://www.paper.edu.cn/releasepaper/content/202605-109.学科分类
基础医学/临床医学
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