自噬对脑卒中的双重作用及针刺干预进展

罗宝春; 刘思凡; 郑佳; 郑蕾; 张柏雯; 尚彤; 尚亚新; 邹伟

doi:10.16766/j.cnki.issn.1674-4152.004423

自噬对脑卒中的双重作用及针刺干预进展

doi: 10.16766/j.cnki.issn.1674-4152.004423

罗宝春¹,
刘思凡¹,
郑佳^{1, 2},
郑蕾²,
张柏雯²,
尚彤¹,
尚亚新¹,
邹伟^2, ,

1.
黑龙江中医药大学研究生院, 黑龙江哈尔滨 150006
2.
黑龙江中医药大学附属第一医院针灸科, 黑龙江哈尔滨 150040

基金项目:

国家自然科学基金面上项目 82074540

详细信息

通讯作者:
邹伟，E-mail: zouwei@hljucm.edu.cn

中图分类号: R743.3 R245
计量
- 文章访问数: 14
- HTML全文浏览量: 9
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2025-05-08
- 网络出版日期: 2026-06-02

The double effect of autophagy on stroke and the progress of acupuncture intervention

1.
Graduate School of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150006, China

摘要

摘要: 脑卒中是一种严重威胁人类健康的恶性脑血管事件，具有高发病率、高致残率、高病死率的特点，对脑卒中发病机制及有效治疗方法的探索是中西医研究的重点和难点。自噬作为真核细胞重要的分解代谢机制，在维持细胞内稳态、应对氧化应激、调节能量代谢等方面发挥关键作用。研究发现，自噬在脑卒中病程中具有双向调控作用：适度自噬有利于清除受损细胞器和蛋白质，维持能量稳态，发挥保护作用；过度或不足的自噬可能促发炎症反应和细胞死亡。此外，在不同的脑卒中病理时期，自噬的作用也存在动态变化。针灸是中国传统医学的瑰宝，已被证实在促进中枢神经系统疾病恢复方面发挥着显著的作用。针刺治疗脑卒中具有安全性高、疗效确切的优势。机制研究表明，针刺可以通过调控自噬关键蛋白，影响多个信号通路，既能促进自噬的正常激活，帮助细胞自我修复，又能抑制过度自噬，减少细胞死亡，从而实现神经保护和功能恢复。针刺对脑卒中的疗效与其动态调节自噬水平密切相关，这种调节作用并非简单的激活或抑制，而是基于疾病阶段、病理类型的对应调节。本文将系统综述自噬在脑卒中中的作用机制，总结针刺调控自噬治疗脑卒中的潜在作用，为针刺治疗脑卒中提供更丰富的理论支持。
- 自噬 /
- 脑卒中 /
- 针刺
Abstract: Stroke is defined as a severe malignant cerebrovascular event that poses a significant threat to human health. It is distinguished by a high incidence, high disability rate and high mortality rate. The exploration of the pathogenesis and effective treatment methods of stroke is a key and challenging focus of both traditional Chinese medicine and Western medicine research. Autophagy, a pivotal degradation and metabolic mechanism in eukaryotic cells, plays a crucial role in maintaining cellular homeostasis, responding to oxidative stress and regulating energy metabolism. Researchers have demonstrated that autophagy exhibits a bidirectional regulatory function in the context of stroke: moderate autophagy is beneficial for clearing damaged organelles and proteins, maintaining energy homeostasis, and exerting protective effects; however, excessive or insufficient autophagy may promote inflammatory responses and cell death. Furthermore, the role of autophagy exhibits dynamic variation across the various pathological stages of stroke. Acupuncture, a fundamental element of traditional Chinese medicine, has been demonstrated to play a substantial role in promoting recovery from central nervous system diseases. Among its advantages are high safety and proven therapeutic efficacy in the treatment of stroke. Mechanistic studies have demonstrated that acupuncture can regulate key autophagy proteins and affect multiple signaling pathways, thus promoting normal autophagy activation to aid cellular self-repair, while also inhibiting excessive autophagy to reduce cell death, achieving neuroprotection and functional recovery. The therapeutic effect of acupuncture on stroke is closely related to its dynamic regulation of autophagy levels. This regulatory process is not simply activation or suppression, but is tailored according to disease stages and pathological types. This review methodically summarizes the mechanisms of autophagy in stroke, and the potential role of acupuncture in regulating autophagy for stroke treatment, with the objective of providing more comprehensive theoretical support for acupuncture therapy in stroke.
- Autophagy /
- Stroke /
- Acupuncture

HTML全文

图 1 自噬过程、分子机制和生理功能

Figure 1. Autophagy process, molecular mechanisms, and physiological functions

下载: 全尺寸图片幻灯片

参考文献(44)

[1]	贾杰. 脑卒中全周期康复的思考与策略[J]. 中国全科医学, 2025, 28(2): 129-134. JIA J. Reflections and strategies for full-cycle stroke rehabilitation[J]. Chinese General Practice, 2025, 28(2): 129-134.
[2]	赵依婷, 秦合伟, 魏霞. 自噬在心血管疾病中的作用及中医药治疗进展[J]. 中国实验方剂学杂志, 2025, 31(7): 284-292. ZHAO Y T, QIN H W, WEI X. Role of autophagy in cardiovascular diseases and traditional chinese medicine treatment: a review[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2025, 31(7): 284-292.
[3]	戴晓红, 于学平, 匡炳霖, 等. 针刺通过c-Jun氨基末端激酶通路调控急性脑出血大鼠自噬水平[J]. 针刺研究, 2023, 48(8): 799-803, 811. DAI X H, YU X P, KUANG B L, et al. Modulation of autophagy in the rats with acute intracerebral hemorrhage by acupuncture based on JNK pathway[J]. Acupuncture Research, 2023, 48(8): 799-803, 811.
[4]	周和成, 冯浩, 赵小琴, 等. 基于巨噬细胞内质网应激-自噬-凋亡调控的补阳还五汤对动脉粥样硬化大鼠VCAM-1及易损斑块的作用机制[J]. 中国老年学杂志, 2025, 45(12): 3007-3011. ZHOU H C, FENG H, ZHAO X Q, et al. The mechanism of Bu Yang Huan Wu Tang in regulating VCAM-1 and vulnerable plaques in atherosclerotic rats through macrophage endoplasmic reticulum stress-autophagy-apoptosis regulation[J]. China Journal of Gerontology, 2025, 45(12): 3007-3011.
[5]	IKEDA S, ZABLOCKI D, SADOSHIMA J. The role of autophagy in death of cardiomyocytes[J]. J Mol Cell Cardiol, 2022, 165: 1-8.
[6]	VARGAS J N S, HAMASAKI M, KAWABATA T, et al. The mechanisms and roles of selective autophagy in mammals[J]. Nat Rev Mol Cell Biol, 2023, 24(3): 167-185. doi: 10.1038/s41580-022-00542-2
[7]	CARINCI M, TESTA B, BORDI M, et al. TFG binds LC3C to regulate ULK1 localization and autophagosome formation[J]. EMBO J, 2021, 40(10): e103563. DOI: 10.15252/embj.2019103563.
[8]	ZHOU Y H, MANGHWAR H, HU W M, et al. Degradation mechanism of autophagy-related proteins and research progress[J]. Int J Mol Sci, 2022, 23(13): 7301. DOI: 10.3390/ijms23137301.
[9]	LEVINE B, KROEMER G. Biological functions of autophagy genes: a disease perspective[J]. Cell, 2019, 176(1-2): 11-42. doi: 10.1016/j.cell.2018.09.048
[10]	MELIA T J, LYSTAD A H, SIMONSEN A. Autophagosome biogenesis: from membrane growth to closure[J]. J Cell Biol, 2020, 219(6): e202002085. DOI: 10.1083/jcb.202002085.
[11]	XIE J, ZHANG Y, LI B, et al. Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke[J]. J Transl Med, 2024, 22(1): 248. DOI: 10.1186/s12967-024-04993-3.
[12]	陆飞宇, 李剑侠, 黄先锋, 等. miR-132靶向FoxO3a抑制细胞自噬在脑出血模型大鼠中的神经保护作用[J]. 脑与神经疾病杂志, 2021, 29(10): 629-634. LU F Y, LI J X, HUANG X F, et al. Neuroprotective effect of miR-132 in rats with intracerebral hemorrhage by targeting FOXO3a and inhibiting autophagy[J]. Journal of Brain and Nervous Diseases, 2021, 29(10): 629-634.
[13]	WANG Y, JIANG L, TIAN J J, et al. miR-210 regulates autophagy through the AMPK/mTOR signaling pathway, reduces neuronal cell death and inflammatory responses, and enhances functional recovery following cerebral hemorrhage in mice[J]. Neurochem Res, 2025, 50(3): 180. DOI: 10.1007/s11064-025-04434-7.
[14]	FU K J, XU W L, LENAHAN C, et al. Autophagy regulates inflammation in intracerebral hemorrhage: enemy or friend?[J]. Front Cell Neurosci, 2022, 16: 1036313. DOI: 10.3389/fncel.2022.1036313.
[15]	DUAN X C, WANG W, FENG D X, et al. Roles of autophagy and endoplasmic reticulum stress in intracerebral hemorrhage-induced secondary brain injury in rats[J]. CNS Neurosci Ther, 2017, 23(7): 554-566. doi: 10.1111/cns.12703
[16]	XIAO L L, ZHENG H P, LI J, et al. Neuroinflammation mediated by NLRP3 inflammasome after intracerebral hemorrhage and potential therapeutic targets[J]. Mol Neurobiol, 2020, 57(12): 5130-5149. doi: 10.1007/s12035-020-02082-2
[17]	BIASIZZO M, KOPITAR-JERALA N. Interplay between NLRP3 inflammasome and autophagy[J]. Front Immunol, 2020, 11: 591803. DOI: 10.3389/fimmu.2020.591803.
[18]	刘爱军, 崔建忠, 王树伟, 等. GSK-3βsiRNA对脑出血大鼠血肿周围组织神经元自噬的影响[J]. 神经解剖学杂志, 2021, 37(3): 335-341. LIU A J, CUI J Z, WANG S W, et al. Effects of the GSK-3β siRNA on neuronal autophagy in brain tissue surrounding hematoma following intracerebral hemorrhage[J]. Chinese Journal of Neuroanatomy, 2021, 37(3): 335-341.
[19]	XU K Z, CHEN C G, WU Y, et al. Advances in miR-132-based biomarker and therapeutic potential in the cardiovascular system[J]. Front Pharmacol, 2021, 12: 751487. DOI: 10.3389/fphar.2021.751487.
[20]	WANG R K, LIANG Z, XUE X Y, et al. Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1[J]. J Cell Mol Med, 2024, 28(1): e18007. DOI: 10.1111/jcmm.18007.
[21]	刘文萍, 刘丽丹, 彭颜晖. lncRNA-H19/IGF1R调控高血压脑出血后脑微血管内皮细胞自噬的机制研究[J]. 广西医科大学学报, 2023, 40(9): 1472-1479. LIU W P, LIU L D, PENG Y H. Mechanism of lncRNA-H19/IGF1R regulating autophagy of brain microvascular endothelial cells after hypertensive intracerebral hemorrhage[J]. Journal of Guangxi Medical University, 2023, 40(9): 1472-1479.
[22]	卜发倩, 张吉发, 帅雯, 等. 自噬在脑缺血中的双重作用及小分子治疗药物的研究进展[J]. 中国科学: 生命科学, 2022, 52(12): 1827-1843. BU F Q, ZHANG J F, SHUAI W, et al. The dual effects of autophagy in cerebral ischemia and small-molecular therapeutic drugs[J]. Scientia Sinica(Vitae), 2022, 52(12): 1827-1843.
[23]	AJOOLABADY A, WANG S Y, KROEMER G, et al. Targeting autophagy in ischemic stroke: from molecular mechanisms to clinical therapeutics[J]. Pharmacol Ther, 2021, 225: 107848. DOI: 10.1016/j.pharmthera.2021.107848.
[24]	CHEN X Y, SHI C R, HE M H, et al. Endoplasmic reticulum stress: molecular mechanism and therapeutic targets[J]. Signal Transduct Target Ther, 2023, 8(1): 352. DOI: 10.1038/s41392-023-01570-w.
[25]	饶欧阳, 李世欣, 朱宁, 等. 6-姜烯酚通过miRNA-26a-5p/DAPK1减轻大鼠脑缺血再灌注损伤[J]. 科学技术与工程, 2024, 24(27): 11594-11603. RAO O Y, LI S X, ZHU N, et al. 6-Shogaol attenuates cerebral ischaemia-reperfusion injury in rats via miRNA-26a-5p/DAPK1[J]. Science Technology and Engineering, 2024, 24(27): 11594-11603.
[26]	周超瑞, 顾健坤, 陈娜, 等. 巴佛洛霉素A1介导AMPK/mTOR/ULK1信号通路对脑缺血再灌注损伤小鼠的神经保护机制研究[J]. 中华全科医学, 2024, 22(2): 225-229. doi: 10.16766/j.cnki.issn.1674-4152.003371 ZHOU C R, GU J K, CHEN N, et al. Neuroprotective effect of Bafilomycin A1 on cerebral ischaemia reperfusion injury by regulation AMPK/mTOR/ULK1 signaling pathway in mice[J]. Chinese Journal of General Practice, 2024, 22(2): 225-229. doi: 10.16766/j.cnki.issn.1674-4152.003371
[27]	SUN X W, LIU H, SUN Z R, et al. Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis[J]. Mol Med, 2020, 26(1): 105. DOI: 10.1186/s10020-020-00236-5.
[28]	刘艳萍, 董强. 组织型激肽释放酶通过诱导自噬对缺血性脑卒中发挥保护作用[J]. 神经损伤与功能重建, 2023, 18(8): 446-449. LIU Y P, DONG Q. Tissue kallikrein exerts a protective effect on ischemic stroke by inducing autophagy[J]. Neural Injury and Functional Reconstruction, 2023, 18(8): 446-449.
[29]	陈笛, 温昌明, 周静, 等. 二氢杨梅素调节HIF-1α/BNIP3信号通路对脑卒中大鼠神经元自噬和凋亡的影响[J]. 中国老年学杂志, 2024, 44(13): 3249-3253. CHEN D, WEN C M, ZHOU J, et al. The effect of dihydrocyanidin on the HIF-1α/BNIP3 signaling pathway on neuronal autophagy and apoptosis in rats with stroke[J]. China Journal of Gerontology, 2024, 44(13): 3249-3253.
[30]	CHEN X D, LIN S Y, GU L, et al. Inhibition of miR-497 improves functional outcome after ischemic stroke by enhancing neuronal autophagy in young and aged rats[J]. Neurochem Int, 2019, 127: 64-72. doi: 10.1016/j.neuint.2019.01.005
[31]	YAO H M, LI J, LIU Z X, et al. Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression[J]. Autophagy, 2023, 19(5): 1491-1511. doi: 10.1080/15548627.2022.2139920
[32]	刚瑛, 丁鹏, 李冰, 等. 麝香酮调节cGAS-STING信号通路对缺血性脑卒中大鼠神经炎症的影响[J]. 中医药导报, 2024, 30(3): 20-24, 42. GANG Y, DING P, LI B, et al. Impact of muscone on neuroinflammation in ischemic stroke rats by regulating the cGAS-STING signaling pathway[J]. Guiding Journal of Traditional Chinese Medicine and Pharmacy, 2024, 30(3): 20-24, 42.
[33]	莫圣龙, 朱海燕, 陆志成, 等. 抑制水通道蛋白4表达对脑缺血再灌注模型小鼠自噬和凋亡的影响[J]. 中国病理生理杂志, 2024, 40(8): 1446-1454. MO S L, ZHU H Y, LU Z C, et al. Impact of inhibiting aquaporin 4 expression on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion[J]. Chinese Journal of Pathophysiology, 2024, 40(8): 1446-1454.
[34]	肖畅, 杨丹, 韦天未, 等. 头皮针联合康复训练对急性脑梗死患者血清MCP-1、ET、sICAM-1水平及神经功能康复的影响[J]. 中华全科医学, 2024, 22(2): 301-303, 320. doi: 10.16766/j.cnki.issn.1674-4152.003389 XIAO C, YANG D, WEI T W, et al. Effect of scalp acupuncture combined with rehabilitation training on serum MCP-1, ET, sICAM-1 content and nerve function rehabilitation in patients[J]. Chinese Journal of General Practice, 2024, 22(2): 301-303, 320. doi: 10.16766/j.cnki.issn.1674-4152.003389
[35]	李莲, 田军, 张秋媛, 等. 补阳还五汤联合醒脑开窍针刺治疗高血压性基底节区脑出血临床研究[J]. 陕西中医, 2025, 46(3): 403-406. LI L, TIAN J, ZHANG Q Y, et al. Clinical study on treatment of hypertensive basal ganglia hemorrhage by Buyang Huanwu decoction combined with Xingnao Kaiqiao acupuncture[J]. Shaanxi Journal of Traditional Chinese Medicine, 2025, 46(3): 403-406.
[36]	WU X L, ZHENG Y R, LIU M R, et al. BNIP3L/NIX degradation leads to mitophagy deficiency in ischemic brains[J]. Autophagy, 2021, 17(8): 1934-1946. doi: 10.1080/15548627.2020.1802089
[37]	邹伟, 刘鹏, 于学平, 等. 头穴透刺法对急性期脑出血大鼠脑组织Beclin1和BNIP3L蛋白表达的影响[J]. 中国中医急症, 2019, 28(6): 950-953. ZOU W, LIU P, YU X P, et al. Effects of scalp acupuncture on Beclin1 and BNIP3L protein expression in rats with acute intracerebral hemorrhage[J]. Journal of Emergency in Traditional Chinese Medicine, 2019, 28(6): 950-953.
[38]	SUN C B, GAO X Y, SHA S, et al. Berberine alleviates Alzheimer ' s disease by activating autophagy and inhibiting ferroptosis through the JNK-p38MAPK signaling pathway[J]. Int Immunopharmacol, 2025, 155: 114550. DOI: 10.1016/j.intimp.2025.114550.
[39]	邹伟, 牛明明, 于学平, 等. "百会"透"曲鬓"针刺法对脑出血大鼠脑组织中PERK蛋白表达影响的实验研究[J]. 中医药信息, 2017, 34(2): 75-79. ZOU W, NIU M M, YU X P, et al. Effect of Baihui-Qubin acupuncture therapy on PERK protein expression in intracerebral hemorrhage rat models[J]. Information on Traditional Chinese Medicine, 2017, 34(2): 75-79.
[40]	刘昊, 阮晨, 杜嘉, 等. 针刺对脑出血大鼠脑组织小胶质细胞自噬的影响[J]. 浙江中医杂志, 2025, 60(5): 377-380. LIU H, RUAN C, DU J, et al. Effects of acupuncture on the regulation of microglia autophagy in rats with hemorrhagic stroke[J]. Zhejiang Journal of Traditional Chinese Medicine, 2025, 60(5): 377-380.
[41]	高静, 赖名殷, 秦玮珣, 等. 针刺对宫内窘迫缺血缺氧脑损伤新生大鼠行为学及海马神经元自噬的影响[J]. 针刺研究, 2020, 45(4): 275-280, 324. GAO J, LAI M Y, QIN W X, et al. Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress[J]. Acupuncture Research, 2020, 45(4): 275-280, 324.
[42]	HUANG Y G, TAO W, YANG S B, et al. Autophagy: novel insights into therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury[J]. Neural Regen Res, 2019, 14(6): 954-961. doi: 10.4103/1673-5374.250569
[43]	杨晶, 杨畅, 王翠, 等. 针刺通过调节自噬反应对脑卒中大鼠的神经元损伤的影响[J]. 中华老年心脑血管病杂志, 2023, 25(2): 188-191. YANG J, YANG C, WANG C, et al. Acupuncture attenuates neuronal damage in stroke rats by regulating autophagy[J]. Chinese Journal of Geriatric Heart, Brain and Vessel Diseases, 2023, 25(2): 188-191.
[44]	WANG M M, ZHANG M, FENG Y S, et al. Electroacupuncture inhibits neuronal autophagy and apoptosis via the PI3K/AKT pathway following ischemic stroke[J]. Front Cell Neurosci, 2020, 14: 134. DOI: 10.3389/fncel.2020.00134.