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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

王汝月¹, 王玥², 韩松¹, 刘月¹, 李俊发¹, 赵丽^1,*

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

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。

关键词： 1型糖尿病; 认知功能障碍; 小胶质细胞

分类号：R322.81

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

WANG Ru-Yue¹, WANG Yue², HAN Song¹, LIU Yue¹, LI Jun-Fa¹, ZHAO Li^1,*

¹Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing 100069, China；²Department of Neurology, Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

Abstract

The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J 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 8th 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 T1DM 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 T1DM mice.

Key words: type 1 diabetes mellitus; cognitive impairment; microglia

收稿日期：2020-03-23　　录用日期：2020-08-17

通讯作者：赵丽　　E-mail: zhaoli@ccmu.edu.cn

DOI: 10.13294/j.aps.2020.0088

引用本文：

王汝月, 王玥, 韩松, 刘月, 李俊发, 赵丽. 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[J]. 生理学报 2021; 73 (1): 10-16.

WANG Ru-Yue, WANG Yue, HAN Song, LIU Yue, LI Jun-Fa, ZHAO Li. Changes in microglia number and Iba1 expression level in the prefrontal cortex of type 1 diabetic mice. Acta Physiol Sin 2021; 73 (1): 10-16 (in Chinese with English abstract).