1型糖尿病小鼠前额叶皮层小胶质细胞数量和Iba1表达水平的变化  

Changes in microglia number and Iba1 expression level in the prefrontal cortex of type 1 diabetic mice

作　　者：王汝月 王玥[2] 韩松[1] 刘月 李俊发[1] 赵丽[1] WANG Ru-Yue;WANG Yue;HAN Song;LIU Yue;LI Jun-Fa;ZHAO Li(Department of Neurobiology,School of Basic Medicine,Capital Medical University,Beijing 100069,China;Department of Neurology,Chao-Yang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学基础医学院神经生物学系,北京100069 [2]首都医科大学附属北京朝阳医院神经内科,北京100020

出　　处：《生理学报》2021年第1期10-16,共7页Acta Physiologica Sinica

基　　金：supported by the Beijing Municipal Natural Science Foundation(No.7192016);Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM201910025029);New Star Project of Chao-Yang Hospital,China(No.CYXX-2017-01)。

摘　　要：本文旨在研究1型糖尿病(type 1 diabetes mellitus,T1DM)小鼠前额叶皮层小胶质细胞的激活情况以及与神经退行性疾病相关的小胶质细胞新亚型(disease-associated microglia,DAM)标志性分子表达的变化。60只健康成年雄性C57BL/6J小鼠,随机分为正常对照(CON)组和T1DM组,每组30只。T1DM组小鼠腹腔注射链脲佐菌素(streptozocin,STZ)建立T1DM模型。模型构建成功后第8周通过Morris水迷宫检测小鼠空间学习记忆能力,通过免疫荧光染色法和Western blot检测小鼠前额叶皮层小胶质细胞数量及激活情况,通过RT-FQ-PCR法检测多个DAM标志性分子mRNA水平的变化。结果显示,与CON组相比,T1DM组小鼠空腹血糖明显升高,体重显著降低,水迷宫逃避潜伏期明显延长,差异均有统计学意义(P<0.05)。与CON组相比,T1DM组小鼠前额叶皮层Iba1蛋白表达水平上调,且小胶质细胞数目明显增多(P<0.05),胞体增大,呈现激活状态。同时,T1DM组小鼠前额叶皮层多个DAM标志性分子mRNA水平显著升高(P<0.05)。以上结果提示,T1DM小鼠前额叶皮层小胶质细胞被激活,且向DAM型转化。The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus(T1 DM)mice,and the expression of the marker genes of the disease-associated microglia(DAM)associated with neurodegenerative diseases.Sixty healthy adult male C57BL/6 J mice were randomly divided into two groups,normal control(CON)group and T1DM group.Streptozocin(STZ)was injected intraperitoneally to induce T1DM mice.The spatial learning and memory function of mice was detected by Morris water maze at the 8 th week after the successful model establishment.The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot.Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR.The results showed that,compared with CON mice,the fasting blood glucose of T1DM mice increased significantly,while the body weight of T1 DM mice decreased remarkably(P<0.05).The escape latency of water maze in T1DM mice was longer than that in CON mice(P<0.05).Compared with CON group,the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly(P<0.05).In addition,the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly(P<0.05).These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1 DM mice.

关 键 词：1型糖尿病 认知功能障碍 小胶质细胞 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]