基础医学与临床 ›› 2024, Vol. 44 ›› Issue (2): 167-173.doi: 10.16352/j.issn.1001-6325.2024.02.0167

• 研究论文 • 上一篇    下一篇

髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用

王曌慧1, 刘潇1, 周玥1, 魏心怡1, 王玥2,3, 李俊发1, 赵丽1*   

  1. 1.首都医科大学 基础医学院 神经生物学系,北京 100006;
    2.首都医科大学附属北京安定医院国家精神心理疾病临床医学研究中心 精神疾病诊断与治疗北京市重点实验室,北京 100088;
    3.首都医科大学 人脑保护高精尖创新中心,北京 100069
  • 收稿日期:2023-11-01 修回日期:2023-12-26 出版日期:2024-02-05 发布日期:2024-02-05
  • 通讯作者: *zhaoli@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金(82071539);北京市自然科学基金(7232003,7222064)

Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia

WANG Zhaohui1, LIU Xiao1, ZHOU Yue1, WEI Xinyi1, WANG Yue2,3, LI Junfa1, ZHAO Li1*   

  1. 1. Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing 100006;
    2. Beijing Key Laboratory of Diagnosis and Treatment of Mental Disorders, National Clinical Medical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088;
    3. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
  • Received:2023-11-01 Revised:2023-12-26 Online:2024-02-05 Published:2024-02-05
  • Contact: *zhaoli@ccmu.edu.cn

摘要: 目的 探索高糖条件下小胶质细胞中髓系细胞触发受体2(triggering receptor expressed on myeloid cells 2, TREM2)的表达情况,以及TREM2在高糖条件下小胶质细胞增殖、迁移和吞噬中的作用。方法 小胶质细胞分为对照组、高糖处理组(67.5 mmol/L葡萄糖,24 h),检测小胶质细胞数量、Iba1和TREM2的表达水平;转染TREM2的siRNA,检测小胶质细胞增殖和迁移能力的变化;加入带有荧光标签的淀粉样蛋白β(Aβ),观察小胶质细胞对Aβ吞噬能力的影响。结果 与正常小胶质细胞相比,高糖处理后小胶质细胞的数量明显下降(P<0.001),而TREM2和Iba1表达显著升高(P<0.001)。高糖和TREM2均不影响小胶质细胞的增殖能力。与正常组相比,高糖处理后小胶质细胞迁移能力下降(P<0.05),而TREM2对高糖小胶质细胞的迁移能力无显著影响。与正常小胶质细胞相比,高糖处理组小胶质细胞对Aβ的吞噬能力显著下降(P<0.001),TREM2 siRNA敲减后高糖小胶质细胞对Aβ的吞噬能力进一步下降(P<0.001)。结论 高糖处理后小胶质细胞TREM2表达明显升高,其主要影响小胶质细胞对Aβ的吞噬能力。

关键词: 高糖, 小胶质细胞, 髓系细胞触发受体2

Abstract: Objective To explore the expression of triggering receptor expressed on myeloid cells 2 (TREM2) in high-glucose microglia and to investigate the role of TREM2 in the proliferation, migration and phagocytosis of high-glucose microglia. Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose, 24 h). The microglia cells were counted and the expression of Iba1 and TREM2 was detected. TREM2 siRNA was transfected to detect the proliferation and migration of microglia. The amyloid β-peptide (Aβ) with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia. Results Compared to normal microglia, the number of microglia significantly decreased after high-glucose treatment (P<0.001), while the expression of TREM2 and Iba1 markedly increased (P<0.001). High glucose and TREM2 did not affect the proliferation of microglia. Compared to the normal group, the migration of microglia significantly decreased after high-glucose treatment (P<0.05) and TREM2 did not affect the migration ability of high-glucose microglia. Compared to the normal group, the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P<0.001). Furthermore, TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia (P<0.001). Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treatment, which significantly affects phagocytosis of Aβ by microglia.

Key words: high glucose, microglia, myeloid cell trigger receptor 2 (TREM2)

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