miR-124在脑缺血再灌注损伤中的研究进展

金子开; 胡滟琦; 张利达; 张君宇; 罗佛赐; 韩为

doi:10.16766/j.cnki.issn.1674-4152.002996

miR-124在脑缺血再灌注损伤中的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.002996

金子开^{1, 2},
胡滟琦³,
张利达⁴,
张君宇⁵,
罗佛赐⁶,
韩为^4, ,

1.
中国中医科学院望京医院脊柱二科，北京 100102
2.
北京中医药大学，北京 100105
3.
安徽中医药大学针灸推拿学院，安徽合肥 230038
4.
广州医科大学附属脑科医院中医科，广东广州 510370
5.
安徽中医药大学第二附属医院老年病三科，安徽合肥 230061
6.
安徽中医药大学研究生院，安徽合肥 230038

基金项目:

国家自然科学基金项目 81973933

安徽省第十三批115产业创新团队项目皖人才办[2020]4号

安徽省中央引导地方科技发展专项 2017070802D151

安徽省教育厅高校优秀拔尖人才培育计划 gxbjZD16

安徽省学术和技术带头人及后备人选学术科研项目 2016H098

安徽中医药大学自然科学基金项目 2020efyzc03

详细信息

通讯作者:
韩为, E-mail: 13956060099@139.com

中图分类号: R743.33
计量
- 文章访问数: 167
- HTML全文浏览量: 137
- PDF下载量: 17
- 被引次数: 0
出版历程
- 收稿日期: 2022-01-10
- 网络出版日期: 2023-07-10

Advances of miR-124 in cerebral ischemia-reperfusion injury

JIN Zikai^{1, 2},
HU Yanqi³,
ZHANG Lida⁴,
ZHANG Junyu⁵,
LUO Foci⁶,
HAN Wei^{4
, ,}

1.
Spine Department, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China

摘要

摘要: 微小核糖核酸(microRNA, miRNA)是一类进化上高度保守的非编码中链小分子RNA，能够参与调节脑缺血再灌注损伤(cerebral ischemia reperfusion injury, CIRI)病理生理过程，被认为是潜在的脑缺血(cerebral ischemia, CI)诊断生物标志物。miR-124是大脑皮层和小脑中优先表达的miRNA，在缺血性脑损伤发生后，miR-124与人体内多个靶点结合，通过调控细胞凋亡、自噬、神经炎症、氧化应激反应、促进神经保护与再生、抑制兴奋性氨基酸毒性等多种机制调节缺血性脑损伤的发展走向，具有一定的神经恢复潜力，且在调控细胞凋亡、神经炎症的过程中具备负向调节作用。但目前有关miR-124调控缺血性脑损伤在临床层面的证据相对匮乏，需要在广泛的临床试验中进一步论证其作为缺血性脑损伤诊断生物标志物、治疗靶点的可能性。
- 脑缺血再灌注损伤 /
- 脑缺血 /
- 微小核糖核酸-124 /
- 生物标志物 /
- 靶点 /
- 综述
Abstract: MicroRNAs (miRNAs) are a class of evolutionarily highly conserved non-coding medium-stranded small molecule RNAs that can participate in regulating the pathophysiological processes of cerebral ischemia-reperfusion injury (CIRI). They are also considered as potential diagnostic biomarkers of cerebral ischemia (CI). miR-124 is a preferentially expressed miRNA in the cerebral cortex and cerebellum, which binds to multiple targets in the body after ischemic brain injury. It regulates the development of ischemic brain injury through various mechanisms such as regulation of apoptosis, autophagy, neuroinflammation, oxidative stress, promotion of neuroprotection and regeneration and inhibition of excitatory amino acid toxicity. In addition, it has a certain potential for neurorestoration by regulating the development of brain injury. Moreover, it has a negative regulatory role in regulating apoptosis and neuroinflammation. However, there is a paucity of evidence on miR-124 regulation of ischemic brain injury at the clinical level. Therefore, its potential as a diagnostic biomarker and therapeutic target for ischemic brain injury needs to be further demonstrated in extensive clinical trials.
- Cerebral ischemia reperfusion injury /
- Cerebral ischemia /
- MicroRNA-124 /
- Biomarkers /
- Targets /
- Review

HTML全文

表 1 miR-124不同表达部位、疾病模型参与调控CIRI的机制

Table 1. miR-124 mechanisms involved in the regulation of CIRI by different expression sites and disease models

miR-124的表达部位/疾病模型	miR-124的直接靶点/通路	效应机制	参考文献
LPS刺激激活的小胶质细胞	p38/p62	miR-124通过靶向p62/p38表达抑制促炎介质的分泌，促进炎症发病机制中的自噬。	[27]
星形胶质细胞	GLT1/EAAT2	神经元细胞核外的miR-124a可以增加星形胶质细胞内GLT1/EAAT2的表达，快速清除突触部位过量的Glu，减少神经元兴奋性氨基酸毒性作用。	[59]
OGD诱导的PC12细胞和大鼠CIRI模型	PI3K/Akt2	miR-124表达下降，负性调控PI3K/Akt2信号通路，可能上调Nrf2在PC12细胞中的表达，减轻神经炎症，保护神经。	[35]
大鼠MACO模型	STAT3	TCZ可以通过激活miR-124介导的STAT3信号通路，减少神经细胞的凋亡。	[5, 20]
	Notch3	电针刺激MACO小鼠，可提高miR-124a靶向的Notch3信号通路相关基因表达水平，改善神经功能恢复，减少脑梗死面积，降低海马神经元凋亡。	[21, 23]
大鼠HIE模型	JAK2/STAT3/Bcl-2	β干扰素通过激活miR-124介导的JAK1/STAT3/Bcl-2通路以保护神经。	[5, 18]

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表 2 miR-124参与调控CIRI的生物学过程

Table 2. miR-124 involved in regulating the biological process of CIRI

miR-124调控CIRI的生物学过程	miR-124的直接靶点/通路	效应机制	参考文献
细胞凋亡	3'UTR	miR-124作用于CREB的3'UTR后引起CREB活化，促进抗凋亡、保护蛋白分子、BDNF等表达，促进神经元再生与修复以保护脑神经。	[16]
	Ku70	敲除脑miR-124可减少细胞死亡和梗死面积，并通过负向调节Ku70改善CIRI导致的神经损伤。	[22]
细胞自噬	PI3K/AKT/mTOR	miR-124负调控PI3K/AKT/mTOR通路，减弱细胞自噬，减轻神经损伤。	[30]
	NF-κB/p53	miR-124可通过NF-κB/p53通路降低p53的表达，抑制自噬，促进脑卒中和脑损伤的神经元细胞存活。	[32]
神经炎症	TLR4	miR-124-3p直接作用于SPTLC2，调节TLR4信号通路，阻止MyD88的招募及NF-κB激活，从而减少促炎细胞因子的释放。	[37]
氧化应激	GSK-3β	miR-124可能裂解GSK-3β，抑制其活性来减轻神经元损伤，抵抗OS。	[44-45]
	PI3K/AKT/mTOR	miR-124激活PI3K/AKT/mTOR通路，减轻CIRI诱导的OS等。	[46-47]
促进神经保护与再生	NPs	脑室内递送miR-124负载NPs促进了缺氧缺糖后脑室下区神经干细胞的神经元分化，有助于脑卒中后神经突触形成和行为恢复。	[50]
	Usp14	miR-124直接靶向抑制Usp14，介导REST的降低，且能将小胶质细胞/巨噬细胞转变为M2抗炎表型以释放抗炎因子，并激活调节性T细胞，增强神经元分化和神经血管重塑。	[4, 54]
抑制兴奋性氨基酸毒性	Akt/mTOR	miR-124通过Akt和mTOR途径调节OGD/再灌注后星形胶质细胞GLT-1的表达，清除突触部位过量Glu，防止中枢神经系统细胞外Glu过度积累。	[59]

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