环状RNA对缺血性卒中调控作用的研究进展

doi:10.3877/cma.j.issn.1673-9248.2025.06.013

缺血性卒中作为全球致残和致死的主要病因，其病理生理机制复杂，但静脉溶栓及机械取栓等治疗手段受限于严格的时间窗和适用范围，故亟须探索新型干预靶点。近年来，环状RNA（circRNA）因其高度稳定性、组织特异性及多靶点调控能力，逐渐成为缺血性卒中诊断和治疗的研究热点。因此，本文拟就circRNA在调节星形胶质细胞功能和神经元炎症损伤、调控细胞凋亡及铁死亡、调节脑血管功能与卒中后血管修复、影响内皮细胞功能与血脑屏障等关键环节中的调控作用进行综述，以指导进一步研究开展，探索改善缺血性卒中的治疗新靶点。

关键词: 环状RNA, 缺血性卒中, 信号通路, 生物标志物, 基因组学

Ischemic stroke, as a major cause of disability and mortality worldwide, has a complex pathophysiological mechanism. However, current treatments such as intravenous thrombolysis and mechanical thrombectomy remain limited by narrow time windows and restricted eligibility. Therefore, it is urgent to explore new intervention targets. In recent years, circular RNA (circRNA) has gradually become a promising focus in the diagnosis and treatment of ischemic stroke due to its high stability, tissue specificity, and ability to regulate multiple pathways. Therefore, this article summarizes the regulatory role of circRNA in key links such as regulating astrocyte function and neuronal inflammatory injury, regulating apoptosis and ferroptosis, regulating cerebrovascular function and post-stroke vascular repair, and influencing endothelial cell function and blood-brain barrier integrity, in order to guide further research and explore new therapeutic targets for improving ischemic stroke.

Key words: Circular RNA, Ischemic stroke, Signaling pathways, Biomarkers, Genomics

图1 环状RNA（circRNA）在缺血性卒中中的调控作用注：miRNA为微RNA；mRNA为信使RNA

表1 缺血性卒中中主要circRNA及其功能

保护性			促损伤性
circRNA名称	靶向miRNA/通路	功能简述	circRNA名称	靶向miRNA/通路	功能简述
circCNOT6L^［6］	miR-99a-5p/SERPINE1	抑制星形胶质细胞凋亡，减轻缺血性卒中损伤	circMap2k1^［11-12］	miR-135b-5p/Pidd1	促进小胶质细胞活化，加重炎症反应
circ_0000115^［7］	miR-1224-5p/NOS3	减少神经元炎症和氧化应激	circNup188^［13］	miR-760-3p/Map3k8	激活NF-κB炎症通路，加重神经炎症
circ_0000831^［8］	miR-16-5p/AdipoR2	减少神经炎症损伤	circZfp609^［14］	miR-145a-5p/BACH1	促进星形胶质细胞凋亡
circPUM1^［9］	miR-340-5p/DDX5	减轻神经元损伤和炎症	circ_0029941^［15］	miR-224-5p/NFAT5	促进星形胶质细胞活化和自噬
circDLGAP4^［10］	miR-503-3p/NEGR1	促进细胞活力，抑制细胞死亡和炎症	circ0001679^［16］	miR-216/TLR4	促进神经元炎症和氧化应激
circRNA_0000964^［23］	miR-758-3p/ILK	抑制Caspase-3介导的神经元凋亡	circPTP4A2^［17］	STAT3	促进小胶质细胞极化，加重神经炎症
circAnks1b^［24］	miR-130b-5p/Pak2	减少内质网应激和神经元凋亡	circ_0101874^［19］	miR-335-5p/PDE4D	促进神经元炎症、凋亡和氧化应激
circPRDX3^［25］	miR-641/NPR3	提高细胞存活率，减少凋亡和梗死体积	circ_22232^［20］	miR-847-3p/Bmp1	促进中性粒细胞激活和炎症因子产生
circBBS2^［26］	miR-494/SLC7A11	抑制铁死亡，减轻缺血性损伤	circLOC375190^［30］	miR-93-5p/mTORC1/TFEB	促进神经元凋亡和自噬
circ_0008146^［27］	miR-342-5p/ACSL4	促进铁死亡和氧化应激	circCRIM1^［31］	miR-141-3p/TXNIP	促进神经元凋亡
circFOXP1^［28］	STAT3	减少细胞凋亡	circ-Carm1^［32］	miR-3098-3p/ACSL4	促进铁死亡
circRap1b^［29］	Hoxa5/Fam3a	抑制神经元凋亡	circCDC14A^［33］	miR-23a-3p/CXCL12	促进细胞凋亡
circUCK2^［37］	FUS/HECTD1	抑制EMT，改善预后	circRIMS^［34］	miR-96-5p/JAK/STAT1	促进细胞凋亡
circRNA_0003307^［38］	miRNA-191-5p/CDK6	促进血管生成、侵袭和迁移	circ_0000018^［35］	miR-871/BCL2L11	促进细胞凋亡
circSCMH1^［39］	m⁶A甲基化通路	促进血管修复，缓解缺血诱导效应	circHECTD1^［41］	miR-335/NOTCH2	促进EMT
circ_0006768^［45］	miR-222-3p/VEZF1	减轻BBB损伤	circPDS5B^［42］	Runx1/ZNF24/VEGF-A	抑制血管生成
circ-FoxO3^［46］	mTORC1	促进自噬，维持BBB完整性	circPDS5B^［43］	miR-223-3p/NOTCH2	抑制血管新生和修复
circOGDH^［47］	外泌体传递COL4A4	增强BBB完整性	circFKBP3^［48］	miR-766-3p/TRAF3	促进HBMECs功能丧失和炎症
			circRBM33^［49］	miR-6838-5p/PDCD4	促进内皮细胞损伤，破坏BBB
			circ-Memo1^［50］	miR-17-5p/SOS1	促进HBMECs损伤
			circ_0010729^［51］	miR-665/ING5	促进HBMECs凋亡
			circSEC11A^［52］	miR-29a-3p/SEMA3A	促进HBMECs损伤和凋亡
			circ_0005548^［53］	miR-362-3p/ETS1	促进HBMECs损伤

表1 缺血性卒中中主要circRNA及其功能

保护性			促损伤性
circRNA名称	靶向miRNA/通路	功能简述	circRNA名称	靶向miRNA/通路	功能简述
circCNOT6L^［6］	miR-99a-5p/SERPINE1	抑制星形胶质细胞凋亡，减轻缺血性卒中损伤	circMap2k1^［11-12］	miR-135b-5p/Pidd1	促进小胶质细胞活化，加重炎症反应
circ_0000115^［7］	miR-1224-5p/NOS3	减少神经元炎症和氧化应激	circNup188^［13］	miR-760-3p/Map3k8	激活NF-κB炎症通路，加重神经炎症
circ_0000831^［8］	miR-16-5p/AdipoR2	减少神经炎症损伤	circZfp609^［14］	miR-145a-5p/BACH1	促进星形胶质细胞凋亡
circPUM1^［9］	miR-340-5p/DDX5	减轻神经元损伤和炎症	circ_0029941^［15］	miR-224-5p/NFAT5	促进星形胶质细胞活化和自噬
circDLGAP4^［10］	miR-503-3p/NEGR1	促进细胞活力，抑制细胞死亡和炎症	circ0001679^［16］	miR-216/TLR4	促进神经元炎症和氧化应激
circRNA_0000964^［23］	miR-758-3p/ILK	抑制Caspase-3介导的神经元凋亡	circPTP4A2^［17］	STAT3	促进小胶质细胞极化，加重神经炎症
circAnks1b^［24］	miR-130b-5p/Pak2	减少内质网应激和神经元凋亡	circ_0101874^［19］	miR-335-5p/PDE4D	促进神经元炎症、凋亡和氧化应激
circPRDX3^［25］	miR-641/NPR3	提高细胞存活率，减少凋亡和梗死体积	circ_22232^［20］	miR-847-3p/Bmp1	促进中性粒细胞激活和炎症因子产生
circBBS2^［26］	miR-494/SLC7A11	抑制铁死亡，减轻缺血性损伤	circLOC375190^［30］	miR-93-5p/mTORC1/TFEB	促进神经元凋亡和自噬
circ_0008146^［27］	miR-342-5p/ACSL4	促进铁死亡和氧化应激	circCRIM1^［31］	miR-141-3p/TXNIP	促进神经元凋亡
circFOXP1^［28］	STAT3	减少细胞凋亡	circ-Carm1^［32］	miR-3098-3p/ACSL4	促进铁死亡
circRap1b^［29］	Hoxa5/Fam3a	抑制神经元凋亡	circCDC14A^［33］	miR-23a-3p/CXCL12	促进细胞凋亡
circUCK2^［37］	FUS/HECTD1	抑制EMT，改善预后	circRIMS^［34］	miR-96-5p/JAK/STAT1	促进细胞凋亡
circRNA_0003307^［38］	miRNA-191-5p/CDK6	促进血管生成、侵袭和迁移	circ_0000018^［35］	miR-871/BCL2L11	促进细胞凋亡
circSCMH1^［39］	m⁶A甲基化通路	促进血管修复，缓解缺血诱导效应	circHECTD1^［41］	miR-335/NOTCH2	促进EMT
circ_0006768^［45］	miR-222-3p/VEZF1	减轻BBB损伤	circPDS5B^［42］	Runx1/ZNF24/VEGF-A	抑制血管生成
circ-FoxO3^［46］	mTORC1	促进自噬，维持BBB完整性	circPDS5B^［43］	miR-223-3p/NOTCH2	抑制血管新生和修复
circOGDH^［47］	外泌体传递COL4A4	增强BBB完整性	circFKBP3^［48］	miR-766-3p/TRAF3	促进HBMECs功能丧失和炎症
			circRBM33^［49］	miR-6838-5p/PDCD4	促进内皮细胞损伤，破坏BBB
			circ-Memo1^［50］	miR-17-5p/SOS1	促进HBMECs损伤
			circ_0010729^［51］	miR-665/ING5	促进HBMECs凋亡
			circSEC11A^［52］	miR-29a-3p/SEMA3A	促进HBMECs损伤和凋亡
			circ_0005548^［53］	miR-362-3p/ETS1	促进HBMECs损伤

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Research progress on the regulatory role of circular RNAs in ischemic stroke

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Research progress on the regulatory role of circular RNAs in ischemic stroke