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骨髓间充质干细胞源性外泌体促进小胶质细胞/巨噬细胞M2极化抑制急性期脑缺血大鼠炎症反应

孙逸梅, 毛诗慧, 李琳, 江伟锋, 储利胜

孙逸梅, 毛诗慧, 李琳, 江伟锋, 储利胜. 骨髓间充质干细胞源性外泌体促进小胶质细胞/巨噬细胞M2极化抑制急性期脑缺血大鼠炎症反应[J]. 中国药科大学学报, 2023, 54(5): 599-606. DOI: 10.11665/j.issn.1000-5048.2023041703
引用本文: 孙逸梅, 毛诗慧, 李琳, 江伟锋, 储利胜. 骨髓间充质干细胞源性外泌体促进小胶质细胞/巨噬细胞M2极化抑制急性期脑缺血大鼠炎症反应[J]. 中国药科大学学报, 2023, 54(5): 599-606. DOI: 10.11665/j.issn.1000-5048.2023041703
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SUN Yimei, MAO Shihui, LI Lin, JIANG Weifeng, CHU Lisheng. Bone marrow mesenchymal stem cell-derived exosomes promote microglia/macrophage M2 polarization in acute cerebral ischemia rats and inhibit inflammatory response[J]. Journal of China Pharmaceutical University, 2023, 54(5): 599-606. DOI: 10.11665/j.issn.1000-5048.2023041703
Citation: SUN Yimei, MAO Shihui, LI Lin, JIANG Weifeng, CHU Lisheng. Bone marrow mesenchymal stem cell-derived exosomes promote microglia/macrophage M2 polarization in acute cerebral ischemia rats and inhibit inflammatory response[J]. Journal of China Pharmaceutical University, 2023, 54(5): 599-606. DOI: 10.11665/j.issn.1000-5048.2023041703
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骨髓间充质干细胞源性外泌体促进小胶质细胞/巨噬细胞M2极化抑制急性期脑缺血大鼠炎症反应

  • 浙江中医药大学基础医学院，杭州 310053

基金项目: 国家自然科学基金资助项目（No.81274113，No.81873028）；浙江省公益技术应用研究计划资助项目（No.2016C33185）

Bone marrow mesenchymal stem cell-derived exosomes promote microglia/macrophage M2 polarization in acute cerebral ischemia rats and inhibit inflammatory response

  • School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81274113, No.81873028) and the Public Welfare Technology Application Research Project of Zhejiang Province (No.2016C33185)

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  • 摘要: 为探究骨髓间充质干细胞（bone marrow meaenchymal stem cells, BMSCs）源性外泌体（exosomes, Exos）对急性期脑缺血大鼠小胶质细胞/巨噬细胞M1/M2极化的影响，采用超高速离心法分离提取外泌体并鉴定；采用线栓法制备大鼠大脑中动脉阻塞（middle cerebral artery occlusion, MCAO）模型；采用Longa评分和角实验评价大鼠神经功能，2,3,5-氯化三苯基四氮唑（2, 3, 5-triphenyltetrazole chloride, TTC）染色检测大鼠脑梗死体积；采用CD16/32/Iba1、CD206/Iba1免疫荧光双标法检测小胶质细胞/巨噬细胞M1/M2表型；采用RT-qPCR检测大鼠脑缺血周边区CD86、诱导型一氧化氮合酶（inducible nitricoxide synthase, iNOS）、肿瘤坏死因子-α（tumor necrosis factor, TNF-α）、精氨酸酶1（arginase-1, Arg-1）、白细胞介素-10（interleukin-10, IL-10）和转化生长因子β（transforming growth factor beta, TGF-β）的mRNA表达。实验结果表明，BMSC-Exos减少缺血周边区CD16/32+/Iba1+阳性细胞数量（P < 0.01），增加CD206+/Iba1+阳性细胞数量（P < 0.01），减少iNOS、CD86和TNF-α的mRNA表达，增加Arg-1、TGF-β和IL-10的mRNA表达（P < 0.05或P < 0.01）。本研究提示BMSC-Exos调控急性期脑缺血大鼠小胶质细胞/巨噬细胞M1/M2极化，减轻神经炎症，改善脑缺血损伤。
    Abstract: The aim of the present study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the polarization of M1/M2 microglia/macrophages in rats with acute cerebral ischemia.Ultrahigh-speed centrifugation was employed to isolate and identify exosomes; a middle cerebral artery occlusion (MCAO) model was prepared in rats using the intraluminal filament technique; Longa scoring and corner tests were used to evaluate the neurological function of rats; 2, 3, 5-triphenyltetrazole chloride (TTC) staining was used to assess the infarct volume in rat brains; immunofluorescence double-labeling of CD16/32/Iba1 and CD206/Iba1 was performed to detect M1/M2 phenotypes of microglia/macrophages; RT-qPCR was employed to measure the mRNA expression of CD86, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), arginase-1 (Arg-1), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in the ischemic penumbra of rat brains.The experimental results showed that BMSC-Exos reduced the number of CD16/32+/Iba1+ positive cells in the ischemic penumbra (P < 0.01) while increasing the number of CD206+/Iba1+positive cells (P < 0.01), and decreased the mRNA expression of iNOS, CD86, and TNF-α, while increasing the mRNA expression of Arg-1, TGF-β, and IL-10 (P < 0.05 or P < 0.01).This research suggests that BMSC-Exos can regulate M1/M2 polarization of microglia/macrophages in rats with acute cerebral ischemia, alleviate neuroinflammation, and improve ischemic brain injury.
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出版历程
  • 收稿日期:  2023-04-16
  • 修回日期:  2023-10-17
  • 刊出日期:  2023-10-24

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