慢性应激下脑内高糖诱导小鼠海马小胶质细胞M1型极化

M1 MICROGLIAL POLARIZATION INDUCED BY HIGH GLUCOSE IN THE HIPPOCAMPUS OF MICE UNDER CHRONIC STRESS

目的 观察慢性应激下脑内葡萄糖含量对小鼠海马小胶质细胞极化类型的影响,探讨慢性应激致神经炎症的可能机制。方法 采用慢性不可预见温和应激(chronic unpredictable mild stress,CUMS)建立慢性应激小鼠模型,并随机分为对照组、应激组。采用葡萄糖检测试剂盒检测小鼠海马及血浆中葡萄糖含量,RT-PCR和ELISA技术检测海马肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)含量。采用免疫荧光技术检测海马小胶质细胞极化类型。细胞水平采用20μmol/L糖皮质激素(glucocorticoid,GC)和20 mmol/L葡萄糖干预小鼠小胶质细胞系BV2模拟慢性应激及高糖后检测炎性因子IL-6、IL-1β、TNF-α的含量。结果 应激组小鼠海马及血浆中葡萄糖含量均升高;应激组小鼠海马区M1型小胶质细胞标志物CD68表达增加,且TNF-α、IL-1β、IL-6含量均升高;20μmol/L的GC、20mmol/L的葡萄糖干预BV2细胞后IL-6、IL-1β、TNF-α水平均升高,且GC复合葡萄糖与GC组、葡萄糖组比较,IL-6、IL-1β、TNF-α水平均升高。结论 慢性应激诱导脑内高糖,进而促进小鼠海马小胶质细胞M1型极化。[营养学报,2022,44(1):45-51]

Objective To observe the effect of glucose on the types of polarization of hippocampal microglia of mice under chronic stress and explore the possible mechanism of neuroinflammation caused by chronic stress. Methods C57BL/6J mice were randomly divided into control and CUMS groups. Chronic unpredictable mild stress(CUMS) was used to establish a chronic stress model in mice. The glucose content assay kit was used to measure the glucose content in the hippocampus and plasma. The content of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) was measured by means of RT-PCR and ELISA while the types of polarization of hippocampal microglia were detected via Glucocorticoid immunofluorescence. Glucocorticoid(GC, 20 μmol/L) and glucose(20 μmol/L) were used to simulate chronic stress and high glucose in the mouse microglia cell line BV2 culture, and the levels of inflammatory factors IL-6, IL-1β and TNF-α were measured. Results Glucose levels in the hippocampus and plasma in the CUMS group were increased, so was the expression of CD68 in the hippocampus in the CUMS group. The levels of TNF-α, IL-1β and IL-6 were increased, so were the levels of IL-6, IL-1β and TNF-α after 20 μmol/L GC and 20 mmol/L glucose intervention in BV2 cells, and these levels were increased more significantly in GC plus glucose than in GC or glucose alone. Conclusion Chronic stress can induce hyperglycemia in the mouse brain, which promotes M1-type polarization in hippocampal microglia. [ACTA NUTRIMENTA SINICA, 2022, 44(1):45-51]