中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (35): 9206-9216.doi: 10.12307/2026.281

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

MicroRNA-23a-3p调节小胶质细胞极化改善创伤性脑损伤小鼠神经功能

李晓燕1，李静林1，张秋娟1，张晓丽娜2，杨  莉1   

  1. 昆明医科大学第一附属医院，1急诊医学科，2疼痛科，云南省昆明市   650000
  • 收稿日期:2025-09-17 修回日期:2026-01-26 出版日期:2026-12-18 发布日期:2026-04-28
  • 通讯作者: 杨莉，博士，昆明医科大学第一附属医院急诊医学科，云南省昆明市 650000
  • 作者简介:李晓燕，女，1998年生，云南省昭通市人，2025年昆明医科大学毕业，硕士，主要从事急诊医学及中枢神经系统损伤修复相关研究。 共同第一作者：李静林，1982年生，云南省临沧市人，2015年昆明医科大学毕业，硕士，主要从事急危重症医学及中枢神经系统损伤修复的研究。
  • 基金资助:
    云南省科技厅基础研究专项青年项目(202301AU070164)，项目负责人：杨莉；云南省科技厅基础研究专项面上项目(202401AT070067)，项目负责人：张晓丽娜

MicroRNA-23a-3p improves neurological function in mice with traumatic brain injury by regulating microglial polarization

Li Xiaoyan1, Li Jinglin1, Zhang Qiujuan1, Zhang Xiaolina2, Yang Li1   

  1. 1Department of Emergency Medicine, ²Department of Pain Management, First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China
  • Received:2025-09-17 Revised:2026-01-26 Online:2026-12-18 Published:2026-04-28
  • Contact: Yang Li, MD, Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China
  • About author:Li Xiaoyan, MS, Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China Li Jinglin, MS, Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China Li Xiaoyan and Li Jinglin contributed equally to this article.
  • Supported by:
    Young Scientists Fund of Basic Research Special Program of Yunnan Provincial Science and Technology Department, No. 202301AU070164 (to YL); Basic Research Special Program of Yunnan Provincial Science and Technology Department (General Program), No. 202401AT070067 (to ZXLN) 

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摘要：



文题释义：
MicroRNA(microRNA，简称miRNA)：是一类内源性非编码RNA分子，长度为20-24个核苷酸。它通过与靶基因mRNA的3’非翻译区(3’UTR)互补配对，抑制基因表达或促进mRNA降解，从而在转录后水平调控基因表达。miRNA在细胞分化、发育、疾病发生等过程中发挥关键作用，具有高度保守性、组织特异性和时序性，可作为疾病诊断标志物或潜在药物靶点。
创伤性脑损伤：是指由外部物理力量(如撞击、震动、穿透等)作用于头部，导致脑组织结构和功能受损的急性脑损伤。可能引发一系列症状，包括头痛、头晕、恶心、呕吐、意识丧失、认知障碍、情绪波动等，严重程度因损伤类型和部位而异，轻者可能仅短暂影响脑功能，重者可能导致长期残疾甚至死亡。

背景：前期研究表明MicroRNA-23a-3p对创伤性脑损伤具有神经保护潜力，然而，该保护作用是否源于对小胶质细胞M1/M2极化平衡的精准调控，目前缺乏直接证据。
目的：明确创伤性脑损伤后小鼠脑组织MicroRNA-23a-3p的表达变化，探究其调控小胶质细胞极化影响神经功能损伤的具体机制。
方法：将80只C57BL/6J小鼠进行随机分组，设置假手术组，创伤性脑损伤组、创伤性脑损伤+agomir-NC组和创伤性脑损伤+agomir-MicroRNA-23a-3p组。创伤性脑损伤组采用皮质撞击法建立重型创伤性脑损伤小鼠模型，假手术组不做皮质撞击处理，干预组小鼠在造模后给予脑室内注射agomir-NC或agomir-MicroRNA-23a-3p。假手术组与创伤性脑损伤组在造模后1，3，7及14 d分别取6只进行分析，其余2组在造模后14 d每组取6只进行分析。采用改良神经功能缺损评分(mNSS)评估神经损伤程度，苏木精-伊红染色和尼氏染色观察脑组织与神经元病理学的病理变化；qRT-PCR与Western blot检测小鼠脑组织中MicroRNA-23a-3p水平及小胶质细胞M1型(CD16、CD86)和M2型(CD206、精氨酸酶1)标志物表达水平，以及炎症因子肿瘤坏死因子α和白细胞介素10的mRNA及蛋白表达；免疫组织化学染色评估小胶质细胞M1/M2极化状态，并观察损伤区域F4/80阳性细胞的聚集情况。
结果与结论：相较于假手术组，创伤性脑损伤组小鼠脑组织中MicroRNA-23a-3p表达呈损伤早期下调、损伤后7 d开始上调的“V”形曲线改变。上调MicroRNA-23a-3p可降低创伤性脑损伤小鼠mNSS评分；形态学结果显示，上调MicroRNA-23a-3p减轻脑组织水肿和神经元损伤；分子生物学检测结果显示，MicroRNA-23a-3p上调促进小胶质细胞从M1型向M2型极化。结果说明：MicroRNA-23a-3p可通过调节小胶质细胞极化促进小鼠创伤性脑损伤后神经功能恢复。
https://orcid.org/0009-0006-4208-6190 (李晓燕)；https://orcid.org/0000-0002-7897-7618 (李静林)；

https://orcid.org/0000-0001-7273-6525(杨莉) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 创伤性脑损伤, MicroRNA-23a-3p, 小胶质细胞极化, 神经修复, 免疫调节

Abstract: BACKGROUND: Previous studies have demonstrated neuroprotective potential of microRNA-23a-3p in traumatic brain injury. However, direct evidence is still lacking regarding whether this protective effect stems from its precise regulation of the M1/M2 polarization balance of microglia.
OBJECTIVE: To clarify the expression changes of microRNA-23a-3p in mouse brain tissue after traumatic brain injury and to explore the specific mechanism by which it affects neurological function through regulating microglial polarization.
METHODS: Eighty C57BL/6J mice were randomly assigned to four groups: a sham operation group (sham group), a traumatic brain injury group, a traumatic brain injury + agomir-NC group, and a traumatic brain injury + agomir-microRNA-23a-3p group. The traumatic brain injury group used the cortical impact method to establish the severe traumatic brain injury model. The sham group did not undergo cortical impact treatment. The intervention groups were given intraventricular injection of agomir-NC or agomir-microRNA-23a-3p after modeling. For the sham and traumatic brain injury groups, six rats were sampled at 1, 3, 7, and 14 days post-modeling, respectively; six rats from each of the remaining two groups were sampled at 14 days post-modeling. The neurological deficits were evaluated by modified neurological severity score. Hematoxylin-eosin staining and Nissl staining were used to observe the pathological damage of brain tissue and neurons. qRT-PCR and western blot assay were performed to detect the levels of microRNA-23a-3p, the expression of M1 (CD16, CD86) and M2 (CD206, Arginase-1) phenotypic markers in microglia, as well as the mRNA and protein expression of the inflammatory factors tumor necrosis factor-alpha and interleukin-10 in mouse brain tissue. Immunohistochemical staining was used to further assess the M1/M2 polarization status of microglia and to observe the aggregation of F4/80 positive cells in the damaged area.
RESULTS AND CONCLUSION: Compared with the sham group, the expression of microRNA-23a-3p in the brain tissue of the traumatic brain injury group showed a “V” shaped curve change, with downregulation in the early stage of injury and upregulation starting 7 days after the injury. Upregulation of microRNA-23a-3p could reduce the modified neurological severity score of traumatic brain injury mice. Morphological results showed that upregulation of microRNA-23a-3p alleviated brain tissue edema and neuronal damage. Molecular biology detection results showed that upregulation of microRNA-23a-3p promoted microglia polarization from M1 type to M2 type. These findings indicate that microRNA-23a-3p promotes the recovery of neurological function in mice after traumatic brain injury by regulating microglial polarization.


Key words: traumatic brain injury, microRNA-23a-3p, microglial polarization, neural repair, immune regulation

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