靶向组蛋白乙酰化防治缺血性脑卒中的研究进展

doi:10.19586/j.2095-2341.2025.0082

生物技术进展 ›› 2025, Vol. 15 ›› Issue (6): 977-984.DOI: 10.19586/j.2095-2341.2025.0082

靶向组蛋白乙酰化防治缺血性脑卒中的研究进展

王胜利¹(), 陈义汝², 关运祥²()

^1.黄河三门峡医院，河南三门峡 472001
^2.河南中医药大学第一附属医院脑病科，郑州 450000

收稿日期:2025-07-17 接受日期:2025-09-15 出版日期:2025-11-25 发布日期:2026-01-04
通讯作者: 关运祥
作者简介:王胜利 E-mail: 17839977461@163.com；
基金资助:
河南省中医药科学研究专项课题(2024ZY2002);河南省中医药拔尖人才培养项目专项课题(2022ZYBJ06)

Research Advances in Targeting Histone Acetylation for the Prevention and Treatment of Ischemic Stroke

Shengli WANG¹(), Yiru CHEN², Yunxiang GUAN²()

^1.Huanghe Sanmenxia Hospital，Henan Sanmenxia 472001，China
^2.Department of Cerebral Diseases，the First Affiliated Hospital of Henan University of Traditional Chinese Medicine，Zhengzhou 450000，China

Received:2025-07-17 Accepted:2025-09-15 Online:2025-11-25 Published:2026-01-04
Contact: Yunxiang GUAN

摘要/Abstract

摘要：

缺血性脑卒中（ischemic stroke，IS）是一种由于脑血管阻塞或狭窄导致脑部供血不足，从而引起脑组织损害的神经系统疾病，严重影响患者的生存及预后。组蛋白乙酰化由组蛋白乙酰转移酶（histone acetyltransferase，HAT）和组蛋白去乙酰化酶（histone deacetylase，HDAC）动态调控的翻译后修饰，通过调控相关基因表达影响小胶质细胞极化、细胞凋亡及铁死亡等过程，进而干预IS的发病进程。研究表明，通过天然药物、小分子化学药物以及生物技术药物等方式干预组蛋白乙酰化可有效减轻脑细胞损伤，从而实现神经保护作用。综述了组蛋白乙酰化在IS发生发展中的调控机制及其作为IS治疗靶点的潜力，以期为后续IS的临床治疗提供理论参考。

关键词: 缺血性脑卒中, 组蛋白, 乙酰化修饰, 去乙酰化修饰

Abstract:

Ischemic stroke （IS） is a neurological disorder caused by cerebrovascular occlusion or stenosis leading to inadequate cerebral blood supply， resulting in brain tissue damage that severely affects patient survival and prognosis. Histone acetylation， a post-translational modification dynamically regulated by histone acetyltransferase （HAT） and histone deacetylase （HDAC）， influences IS pathogenesis by modulating gene expression related to microglial polarization， apoptosis， and ferroptosis. Studies demonstrate that interventions targeting histone acetylation through natural compounds， small-molecule drugs， and biopharmaceuticals can effectively mitigate neuronal damage and exert neuroprotective effects. This review focused on histone acetylation to elucidate its regulatory mechanisms in IS progression and its potential as a therapeutic target， aiming to provide theoretical foundations for the subsequent clinical IS treatment.

Key words: ischemic stroke, histones, acetylation modification, deacetylation modification

中图分类号:

Q987

王胜利, 陈义汝, 关运祥. 靶向组蛋白乙酰化防治缺血性脑卒中的研究进展[J]. 生物技术进展, 2025, 15(6): 977-984.

Shengli WANG, Yiru CHEN, Yunxiang GUAN. Research Advances in Targeting Histone Acetylation for the Prevention and Treatment of Ischemic Stroke[J]. Current Biotechnology, 2025, 15(6): 977-984.

图/表 5

参考文献 49

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药物名称	组蛋白修饰的调控	作用机制	参考文献
黄芪甲苷Ⅳ	上调H3ac	减少NK细胞脑浸润和活化、抑制炎症反应	[35]
紫檀芪	下调HDAC3	抑制炎症反应	[37]
丹参酮ⅡA	上调H3K18ac、H4K8ac	减轻细胞凋亡和神经兴奋性毒性	[39]
牛蒡叶及其提取物	下调HDAC9	抑制炎症反应	[41]

药物名称	组蛋白修饰的调控	作用机制	参考文献
黄芪甲苷Ⅳ	上调H3ac	减少NK细胞脑浸润和活化、抑制炎症反应	[35]
紫檀芪	下调HDAC3	抑制炎症反应	[37]
丹参酮ⅡA	上调H3K18ac、H4K8ac	减轻细胞凋亡和神经兴奋性毒性	[39]
牛蒡叶及其提取物	下调HDAC9	抑制炎症反应	[41]

药物名称	组蛋白修饰的调控	作用机制	参考文献
丙戊酸	上调H3ac、H4ac	抑制神经胶质瘢痕形成	[42]
伏立诺他	上调H3ac	减弱小胶质细胞活化、缓解BBB功能障碍以及促进脑血管结构-功能重塑	[44]
丁酸钠	上调H3K9ac	抑制炎症反应	[45]

药物名称	组蛋白修饰的调控	作用机制	参考文献
丙戊酸	上调H3ac、H4ac	抑制神经胶质瘢痕形成	[42]
伏立诺他	上调H3ac	减弱小胶质细胞活化、缓解BBB功能障碍以及促进脑血管结构-功能重塑	[44]
丁酸钠	上调H3K9ac	抑制炎症反应	[45]

药物名称	组蛋白修饰的调控	作用机制	参考文献
慢病毒载体携带STAT3 shRNA	下调H3ac、H4ac	抑制炎症反应	[47]
agomir-miR-494	下调HDAC3、上调H3K9ac	减少细胞凋亡，增强轴突可塑性	[48]
H19 siRNA	下调HDAC1、上调H3ac、H4ac	抑制炎症反应	[49]

靶向组蛋白乙酰化防治缺血性脑卒中的研究进展

Research Advances in Targeting Histone Acetylation for the Prevention and Treatment of Ischemic Stroke

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