中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2499-2504.doi: 10.4103/1673-5374.313050

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

芦丁预处理促进小胶质细胞从M1型向M2型转化

  

  • 出版日期:2021-12-15 发布日期:2021-05-15
  • 基金资助:

    遵义市自然科学技术基金(201915);遵义医科大学博士创业基金([2017]5733-045号,[2017]5733-044号);贵州省自然科学技术基金([2020]1992

Rutin pretreatment promotes microglial M1 to M2 phenotype polarization

Guang-Ping Lang1, Can Li1, Ying-Ying Han2, *   

  1. 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou Province, China; 2Special Key Laboratory of Oral Diseases Research, Higher Education Institutions of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou Province, China
  • Online:2021-12-15 Published:2021-05-15
  • Supported by:
    This study was supported by the Natural Science and Technology Foundation of Zunyi City, China, No. 201915 (to GPL); Doctor Startup Foundation of Zunyi Medical University, Nos. [2017]5733-045 (to GPL), [2017]5733-044 (to YYH); and Natural Science and Technology Foundation of Guizhou Province, China, No. [2020]1Y292 (to YYH).

摘要:

小胶质细胞是作为中枢神经系统重要的固有先天免疫成分之一,常在神经炎症中被激活。而小胶质细胞一旦激活,会出现2种不同的表型M1和M2,神经炎症中显示不同的作用。既往研究显示,膳食类黄酮苷芦丁对神经炎症有保护作用,但其是否能影响小胶质细胞M1/M2的极化尚不清楚。此次实验利用100 ng/mL脂多糖刺激BV-2细胞24h建立体外神经炎症模型,观察芦丁预处理1h对小胶质细胞极化的作用。(1)芦丁可降低细胞炎症递质肿瘤坏死因子α、白细胞介素1β及白细胞介素6的表达,同时明显增强白细胞介素10的分泌。同时其还下调了M1小胶质细胞相关标志物CD86和诱导型一氧化氮合酶的表达,并上调M2小胶质细胞相关标志物精氨酸酶1和CD206的表达;(2)芦丁预处理还可抑制Toll样受体4和MyD88表达,并阻断IKK和核因子κB的磷酸化;(3)芦丁可通过抑制Toll样受体4/核因子κB信号通路促进小胶质细胞从M1型向M2型的转化,从而减轻脂多糖诱导的神经炎症。

https://orcid.org/0000-0001-8426-0771 (Ying-Ying Han)

关键词: 芦丁, 神经炎症, M1型小胶质细胞, M2型小胶质细胞, 小胶质细胞极化, 小胶质细胞活化, BV-2细胞, Toll样受体4, 促炎因子, 类黄酮

Abstract: Microglial cells are important resident innate immune components in the central nervous system that are often activated during neuroinflammation. Activated microglia can display one of two phenotypes, M1 or M2, which each play distinct roles in neuroinflammation. Rutin, a dietary flavonoid, exhibits protective effects against neuroinflammation. However, whether rutin is able to influence the M1/M2 polarization of microglia remains unclear. In this study, in vitro BV-2 cell models of neuroinflammation were established using 100 ng/mL lipopolysaccharide to investigate the effects of 1-hour rutin pretreatment on microglial polarization. The results revealed that rutin pretreatment reduced the expression of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 and increased the secretion of interleukin-10. Rutin pretreatment also downregulated the expression of the M1 microglial markers CD86 and inducible nitric oxide synthase and upregulated the expression of the M2 microglial markers arginase 1 and CD206. Rutin pretreatment inhibited the expression of Toll-like receptor 4 and myeloid differentiation factor 88 and blocked the phosphorylation of I kappa B kinase and nuclear factor-kappa B. These results showed that rutin pretreatment may promote the phenotypic switch of microglia M1 to M2 by inhibiting the Toll-like receptor 4/nuclear factor-kappa B signaling pathway to alleviate lipopolysaccharide-induced neuroinflammation. 

Key words: BV-2 cells, flavonoid, M1 microglia, M2 microglia, microglia activation, microglia polarization, neuroinflammation, proinflammatory cytokines, rutin, TLR-4 signaling

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