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。
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 amyloidβ-peptide(Aβ)with a fluorescent tag was added to observe the phagocytosis of Aβby 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 Aβby microglia significantly decreased in the high-glucose treated group(P<0.001).Furthermore,TREM2 knockdown further decreased the phagocytosis of Aβby high-glucose microglia(P<0.001).Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treatment,which significantly affects phagocytosis of Aβby microglia.
作者
王曌慧
刘潇
周玥
魏心怡
王玥
李俊发
赵丽
WANG Zhaohui;LIU Xiao;ZHOU Yue;WEI Xinyi;WANG Yue;LI Junfa;ZHAO Li(Department of Neurobiology,School of Basic Medicine,Capital Medical University,Beijing 100006;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;Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100069,China)
出处
《基础医学与临床》
2024年第2期167-173,共7页
Basic and Clinical Medicine
基金
国家自然科学基金(82071539)
北京市自然科学基金(7232003,7222064)。
关键词
高糖
小胶质细胞
髓系细胞触发受体2
high glucose
microglia
myeloid cell trigger receptor 2(TREM2)
