miR-let-7f减轻小胶质细胞氧糖剥夺诱导的炎症反应及其机制

doi:10.3969/j.issn.1006-5725.2026.17.008

摘要/Abstract

摘要：

目的探讨miR-let-7f在小胶质细胞氧糖剥夺诱导的炎症反应中的调控作用及潜在机制。方法培养小鼠小胶质细胞系BV2并构建细胞氧糖剥夺/复氧（OGD/R）模型，设计并合成miR-let-7f模拟物（mimics）与抑制剂（inhibitor）。分别用实时定量PCR（qPCR）及酶联免疫吸附测定（ELISA）检测各处理组细胞miR-let-7f、高迁移率族蛋白A2（high mobility group AT-hook 2，HMGA2）及炎症因子水平；细胞免疫荧光观察细胞定位与活化。结果 miR-let-7f mimics和inhibitor分别显著上调和下调BV2细胞miR-let-7f的表达（P < 0.000 1）。细胞OGD/R促进促炎蛋白HMGA2和炎症因子肿瘤坏死因子-α（tumor necrosis factor-alpha，TNF-α）、白细胞介素-1β（interleukin-1 beta，IL-1β）表达增多（P < 0.05），并伴NF-κB p65入核增加。miR-let-7f mimics干预后HMGA2及炎症因子水平显著降低（P < 0.05），NF-κB p65入核减少；加入miR-let-7f inhibitor后，上述抑制效应明显减弱（P < 0.05）。结论 miR-let-7f在BV2细胞OGD/R模型中具有抑制炎症作用，其机制可能与调控HMGA2表达、抑制NF-κB信号通路有关。本研究为脑缺血缺氧相关神经炎症的靶向干预提供实验依据。

关键词: 氧糖剥夺, miR-let-7f, 炎症反应, 核因子κB

Abstract:

Objective This study aims to investigate the regulatory effect of miR-let-7f on oxygen-glucose deprivation-induced inflammatory responses in microglia and its underlying molecular mechanism. Methods The murine microglial cell line BV2 was cultured to establish an oxygen-glucose deprivation/reoxygenation （OGD/R） cell model. miR-let-7f mimics and inhibitors were designed and synthesized. Quantitative real-time PCR （qPCR） and enzyme-linked immunosorbent assay （ELISA） were employed to quantify the expression levels of miR-let-7f， high mobility group AT-hook 2 （HMGA2）， and inflammatory cytokines across all treatment groups. Cellular immunofluorescence staining was conducted to visualize the subcellular localization and activation status of microglia. Results Transfection with miR-let-7f mimics and inhibitor significantly upregulated and downregulated miR-let-7f expression in BV2 cells， respectively （P < 0.000 1）. OGD/R treatment increased the expression of the pro-inflammatory protein HMGA2 and the inflammatory cytokines tumor necrosis factor-alpha （TNF-α） and interleukin-1 beta （IL-1β）（P < 0.05）， accompanied by increased nuclear translocation of NF-κB p65. Treatment with miR-let-7f mimics significantly reduced HMGA2 and inflammatory cytokine levels （P < 0.05） and decreased NF-κB p65 nuclear translocation. Following the addition of the miR-let-7f inhibitor， these inhibitory effects were significantly attenuated （P < 0.05）. Conclusions miR-let-7f exerts anti-inflammatory effects in BV2 microglia under OGD/R conditions. This bioactivity may be mediated via the regulation of HMGA2 expression and subsequent suppression of the NF-κB signaling pathway. The present study provides robust experimental evidence for the intervention of neuroinflammation secondary to cerebral ischemia and hypoxia.

Key words: oxygen-glucose deprivation, miR-let-7f, inflammation, nuclear factor kappa B

中图分类号:

R743

吴婵姬, 李虞蒙, 陈恩悦, 黄仕雄. miR-let-7f减轻小胶质细胞氧糖剥夺诱导的炎症反应及其机制[J]. 实用医学杂志, 2026, 42(17): 3103-3110.

Chanji Wu, Yumeng Li, Enyue Chen, Shixiong Huang. miR-let-7f attenuates oxygen-glucose deprivation/reoxygenation-induced inflammatory responses in microglia and the underlying mechanism[J]. The Journal of Practical Medicine, 2026, 42(17): 3103-3110.

图/表 1

参考文献 21

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基因	F（5′-3′）	R（5′-3′）	扩增产物长度/bp
GAPDH	AAGAAGGTGGTGAAGCAGG	GAAGGTGGAAGAGTGGGAGT	111
HMGA2	AAAGACCGCAGTACCACTTACC	GAGATGGCAGTCCGAACCA	117
IL⁃1β	GGGCTGGACTGTTTCTAATGC	CTTGTGACCCTGAGCGACC	128
TNF⁃α	TTAGAAAGGGGATTATGGCTCA	TTTGCAGAACTCAGGAATGGAC	182
IL6	ACAACCACGGCCTTCCCTA	CATTTCCACGATTTCCCAGA	135
COX2	CTGCCAATAGAACTTCCAATCC	CCATAGAATAATCCTGGTCGGT	152
Nos2	CGTTCCTGGAGGTGCTTGA	TCTCGGGTGCGGTAGGTG	169