1.河南中医药大学康复医学院,郑州 450046
2.河南中医药大学第二附属医院康复科,郑州 450002
Received:24 March 2026,
Revised:2026-04-24,
Accepted:28 April 2026,
Published:28 May 2026
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Wang Enhui,Qin Hewei.Research advances in the role of exosomal miRNA in ischemic stroke and its modulation by traditional Chinese medicine[J].Journal of Chongqing Medical University,
Wang Enhui,Qin Hewei.Research advances in the role of exosomal miRNA in ischemic stroke and its modulation by traditional Chinese medicine[J].Journal of Chongqing Medical University, DOI:10.13406/j.cnki.cyxb..
缺血性脑卒中(ischemic stroke,IS)是由于脑动脉急性闭塞或狭窄导致的脑血流中断的脑血管疾病,其高致残率与致死率对公共健康构成严重威胁。近年来,外泌体作为细胞间信息交流的重要载体,在中枢神经系统疾病中的作用逐渐受到关注。外泌体中富含微小核糖核酸(micro ribonucleic acid,miRNA)、长链非编码核糖核酸(long non-coding ribonucleic acid,lncRNA)、环状核糖核酸(circular ribonucleic acid,circRNA)及多种核酸和蛋白质,能够跨越血脑屏障实现远距离信号传递,在抑制神经炎症、促进血管生成、促进神经修复及调控程序性细胞死亡等方面发挥关键作用。同时,中医药干预可通过调控外泌体中miRNA的表达,从多靶点、多通路发挥神经保护作用。本文就外泌体miRNA在IS中的主要作用机制进行系统梳理,并总结中医药调控外泌体miRNA的研究进展,以期为IS的精准诊疗及新型干预策略的制定提供理论依据。
Ischemic stroke(IS) is a cerebrovascular disease characterized by the interruption of cerebral blood flow due to acute occlusion or stenosis of cerebral arteries,and its high disability and mortality rates pose a serious threat to public health. In recent years,exosomes,as important carriers of intercellular communication,have gradually gained attention for their role in central nervous system diseases. Exosomes are rich in miRNAs,lncRNAs,circRNAs,and various nucleic acids and proteins,and by crossing the blood-brain barrier,they enable long-distance signal transmission and play a key role in inhibiting neuroinflammation,promoting angiogenesis and neural repair,and regulating programmed cell death. Meanwhile,traditional Chinese medicine interventions exert a neuroprotective effect through multiple targets and pathways by regulating the expression of exosomal miRNAs. This article systematically reviews the main mechanisms of action of exosomal miRNAs in IS and summarizes the research advances in the regulation of exosomal miRNAs by traditional Chinese medicine,in order to provide a theoretical basis for the precise diagnosis and treatment of IS and the development of novel intervention strategies.
国家卫生健康委加强脑卒中防治工作减少百万新发残疾工程专家委员会 , 吉训明 . 《2024年中国脑卒中防治报告》概要 [J ] . 首都医科大学学报 , 2025 , 46 ( 6 ): 947 - 960 .
Stroke Prevention Project,National Health Commission,Ji XM . Brief report on stroke prevention and treatment in China,2024 [J ] . Journal of Capital Medical University , 2025 , 46 ( 6 ): 947 - 960 .
DeLong JH , Ohashi SN , O’Connor KC , et al . Inflammatory responses after ischemic stroke [J ] . Semin Immunopathol , 2022 , 44 ( 5 ): 625 - 648 .
霍晓川 , 高峰 . 急性缺血性卒中血管内治疗中国指南2023 [J ] . 中国卒中杂志 , 2023 , 18 ( 6 ): 684 - 711 .
Huo XC , Gao F . Chinese Guideline for Endovascular Treatment of Acute Ischemic Stroke 20233 [J ] . Chinese Journal of Stroke , 2023 , 18 ( 6 ): 684 - 711 .
Luo LJ , Hu QR , Yan RJ , et al . Alpha-asarone ameliorates neuronal injury after ischemic stroke and hemorrhagic transformation by attenuating blood-brain barrier destruction,promoting neurogenesis,and inhibiting neuroinflammation [J ] . Mol Neurobiol , 2025 , 62 ( 4 ): 5252 - 5272 .
Li JR , Song JH , Jia LN , et al . Exosomes in central nervous system diseases: a comprehensive review of emerging research and clinical frontiers [J ] . Biomolecules , 2024 , 14 ( 12 ): 1519 .
Li P , Hong GH , Zhan WQ , et al . Endothelial progenitor cell derived exosomes mediated miR-182-5p delivery accelerate diabetic wound healing via down-regulating PPARG [J ] . Int J Med Sci , 2023 , 20 ( 4 ): 468 - 481 .
Valadi H , Ekström K , Bossios A , et al . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells [J ] . Nat Cell Biol , 2007 , 9 ( 6 ): 654 - 659 .
van Niel G , D’Angelo G , Raposo G . Shedding light on the cell biology of extracellular vesicles [J ] . Nat Rev Mol Cell Biol , 2018 , 19 ( 4 ): 213 - 228 .
Kalluri R , LeBleu VS . The biology,function,and biomedical applications of exosomes [J ] . Science , 2020 , 367 ( 6478 ): eaau6977 .
Chen YF , Luh F , Ho YS , et al . Exosomes: a review of biologic function,diagnostic and targeted therapy applications,and clinical trials [J ] . J Biomed Sci , 2024 , 31 ( 1 ): 67 .
Shang RF , Lee S , Senavirathne G , et al . microRNAs in action: biogenesis,function and regulation [J ] . Nat Rev Genet , 2023 , 24 ( 12 ): 816 - 833 .
Bofill-De Ros X , Vang Ørom UA . Recent progress in miRNA biogenesis and decay [J ] . RNA Biol , 2024 , 21 ( 1 ): 1 - 8 .
Agarwal U , George A , Bhutani S , et al . Experimental,systems,and computational approaches to understanding the microRNA-mediated reparative potential of cardiac progenitor cell–derived exosomes from pediatric patients [J ] . Circ Res , 2017 , 120 ( 4 ): 701 - 712 .
Liu LY , Chen SR , Liang SL , et al . The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion [J ] . Mamm Genome , 2024 , 35 ( 3 ): 362 - 376 .
Pan QW , Wang Y , Liu JH , et al . MiR-17-5p mediates the effects of ACE2-enriched endothelial progenitor cell-derived exosomes on ameliorating cerebral ischemic injury in aged mice [J ] . Mol Neurobiol , 2023 , 60 ( 6 ): 3534 - 3552 .
Li R , Liu WC , Yin J , et al . TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3/STAT3 pathway [J ] . J Neuroinflammation , 2018 , 15 ( 1 ): 231 .
Yi F , Xiao H , Song MY , et al . BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1 [J ] . Neurosci Res , 2024 , 199 : 36 - 47 .
Zhao YM , Gan YX , Xu GW , et al . Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation [J ] . Life Sci , 2020 , 260 : 118403 .
Liu XB , Ma HY , Fei LY , et al . HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer [J ] . Infect Agent Cancer , 2020 , 15 : 6 .
Cuomo O , Anzilotti S , Brancaccio P , et al . Systemic administration of blood-derived exosomes induced by remote ischemic post-conditioning,by delivering a specific cluster of miRNAs,ameliorates ischemic damage and neurological function [J ] . J Cereb Blood Flow Metab , 2024 , 44 ( 12 ): 1459 - 1471 .
Liu WT , Shen YJ , Pan RC , et al . miR-330-5p from mesenchymal stem cell-derived exosomes targets SETD7 to reduce inflammation in rats with cerebral ischemia-reperfusion injury [J ] . J Mol Histol , 2024 , 56 ( 1 ): 63 .
Bhattacharya D , Chaudhuri S , Singh MK , et al . T11TS inhibits Angiopoietin-1/Tie-2 signaling,EGFR activation and Raf/MEK/ERK pathway in brain endothelial cells restraining angiogenesis in glioma model [J ] . Exp Mol Pathol , 2015 , 98 ( 3 ): 455 - 466 .
Melincovici C S , Boşca A B , Şuşman S , et al . Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis [J ] . Rom J of Morphol Embryol , 2018 , 59 ( 2 ): 455 - 467 .
Hu H , Hu XW , Li L , et al . Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis in ischemic stroke mice via upregulation of miR-21-5p [J ] . Biomolecules , 2022 , 12 ( 7 ): 883 .
Cao YS , Sun J , Guo LC , et al . Leech extract enhances the pro-angiogenic effects of endothelial cell-derived exosomes in a mouse model of ischemic stroke [J ] . Curr Issues Mol Biol , 2025 , 47 ( 7 ): 499 .
Wang JJ , Chen SZ , Zhang WF , et al . Exosomes from miRNA-126-modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke [J ] . CNS Neurosci Ther , 2020 , 26 ( 12 ): 1255 - 1265 .
Shiojima I , Walsh K . Role of Akt signaling in vascular homeostasis and angiogenesis [J ] . Circ Res , 2002 , 90 ( 12 ): 1243 - 1250 .
Bao HY , Mao SH , Hu XW , et al . Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway [J ] . Sci Rep , 2024 , 14 : 18086 . i
Costa-Mattioli M , Sossin WS , Klann E , et al . Translational control of long-lasting synaptic plasticity and memory [J ] . Neuron , 2009 , 61 ( 1 ): 10 - 26 .
Sim SE , Bakes J , Kaang BK . Neuronal activity-dependent regulation of microRNAs [J ] . Mol Cells , 2014 , 37 ( 7 ): 511 - 517 .
Li SS , Wu JJ , Xing XX , et al . Focal ischemic stroke modifies microglia-derived exosomal miRNAs: potential role of mir-212-5p in neuronal protection and functional recovery [J ] . Biol Res , 2023 , 56 ( 1 ): 52 .
Zhang Y , Liu ZW , Chopp M , et al . Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery [J ] . Neural Regen Res , 2025 , 20 ( 1 ): 224 - 233 .
Hou HQ , Wang YF , Yang L , et al . Exosomal miR-128-3p reversed fibrinogen-mediated inhibition of oligodendrocyte progenitor cell differentiation and remyelination after cerebral ischemia [J ] . CNS Neurosci Ther , 2023 , 29 ( 5 ): 1405 - 1422 .
Xin HQ , Katakowski M , Wang FJ , et al . MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats [J ] . Stroke , 2017 , 48 ( 3 ): 747 - 753 .
Luo HC , Ye GB , Liu Y , et al . miR-150-3p enhances neuroprotective effects of neural stem cell exosomes after hypoxic-ischemic brain injury by targeting CASP2 [J ] . Neurosci Lett , 2022 , 779 : 136635 .
Yu YH , Zhou H , Xiong YQ , et al . Exosomal miR-199a-5p derived from endothelial cells attenuates apoptosis and inflammation in neural cells by inhibiting endoplasmic reticulum stress [J ] . Brain Res , 2020 , 1726 : 146515 .
Yang XY , Xu J , Lan SH , et al . Exosomal miR-133a-3p derived from BMSCs alleviates cerebral ischemia-reperfusion injury via targeting DAPK2 [J ] . Int J Nanomedicine , 2023 , 18 : 65 - 78 .
Wang YJ , Chen HP , Fan XH , et al . Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2 [J ] . J Stroke Cerebrovasc Dis , 2023 , 32 ( 8 ): 107235 .
Zhuo BF , Qin CY , Deng SZ , et al . The role of ACSL4 in stroke: mechanisms and potential therapeutic target [J ] . Mol Cell Biochem , 2025 , 480 ( 4 ): 2223 - 2246 .
Huang MD , Cheng SM , Li ZW , et al . Preconditioning exercise inhibits neuron ferroptosis and ameliorates brain ischemia damage by skeletal muscle-derived exosomes via regulating miR-484/ACSL4 axis [J ] . Antioxid Redox Signal , 2024 , 41 ( 13/14/15 ): 769 - 792 .
Wang Y , Niu HC , Li LY , et al . Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis [J ] . J Nanobiotechnology , 2023 , 21 ( 1 ): 109 .
Niu MY , Li H , Li X , et al . Circulating exosomal miRNAs as novel biomarkers perform superior diagnostic efficiency compared with plasma miRNAs for large-artery atherosclerosis stroke [J ] . Front Pharmacol , 2021 , 12 : 791644 .
Xu C , Yu HL , Chen BL , et al . Serum exosomal mir-340-5p promotes angiogenesis in brain microvascular endothelial cells during oxygen-glucose deprivation [J ] . Neurochem Res , 2022 , 47 ( 4 ): 907 - 920 .
Ji QH , Ji YH , Peng JW , et al . Increased brain-specific miR-9 and miR-124 in the serum exosomes of acute ischemic stroke patients [J ] . PLoS One , 2016 , 11 ( 9 ): e0163645 .
Song P , Sun HQ , Chen HP , et al . Decreased serum exosomal miR-152-3p contributes to the progression of acute ischemic stroke [J ] . Clin Lab , 2020 , 66 ( 8 ).
Qi Z , Zhao YY , Su Y , et al . Serum extracellular vesicle–derived miR-124-3p as a diagnostic and predictive marker for early-stage acute ischemic stroke [J ] . Front Mol Biosci , 2021 , 8 : 685088 .
Ding WL , Gu QC , Liu MM , et al . Astrocytes-derived exosomes pre-treated by berberine inhibit neuroinflammation after stroke via miR-182-5p/Rac1 pathway [J ] . Int Immunopharmacol , 2023 , 118 : 110047 .
Wang ML , Yang YT , Guo YL , et al . Xiaoxuming decoction cutting formula reduces LPS-stimulated inflammation in BV-2 cells by regulating miR-9-5p in microglia exosomes [J ] . Front Pharmacol , 2023 , 14 : 1183612 .
Wei W , Li HH , Deng YF , et al . The combination of Alisma and Atractylodes ameliorates cerebral ischaemia/reperfusion injury by negatively regulating astrocyte-derived exosomal miR-200a-3p/141-3p by targeting SIRT1 [J ] . J Ethnopharmacol , 2023 , 313 : 116597 .
Xu SY , Ni SM , Zeng CL , et al . Electro-acupuncture promotes angiogenesis via exosomal miR-210 in the hypoxia-induced HUVECs mediated HIF-1α/VEGF/Notch 1 signal pathway [J ] . Curr Neurovasc Res , 2022 , 19 ( 4 ): 406 - 417 .
Mao SH , Lan T , Sun YM , et al . Extracellular vesicles enriched with miR-486 from Tetramethylpyrazine-preconditioned bone marrow mesenchymal stem cells promote microglia/macrophage M2 polarization and enhance neurogenesis in rats with ischemic stroke [J ] . Stem Cell Res Ther , 2025 , 16 ( 1 ): 455 .
Zhao DF , Zhao CS , Wang AN , et al . Ginkgolide B attenuates post-stroke cognitive impairment via exosomal miR-299a-3p regulation of the TRIL/PI3K/AKT pathway [J ] . Int Immunopharmacol , 2026 , 176 : 116479 .
Wu CX , Zhao LJ , Li XR , et al . Integrated bioinformatics analysis of potential mRNA and miRNA regulatory networks in mice with ischemic stroke treated by electroacupuncture [J ] . Front Neurol , 2021 , 12 : 719354 .
Zhang SH , Jin TT , Wang LL , et al . Electro-acupuncture promotes the differentiation of endogenous neural stem cells via exosomal microRNA 146b after ischemic stroke [J ] . Front Cell Neurosci , 2020 , 14 : 223 .
Nan YN , Zhu WH , Zhu B , et al . Gastrodin facilitates recovery of neurological function of MCAO rats through upregulating miR-20a-5p/XIAP pathway via exosome [J ] . Neuroreport , 2023 , 34 ( 14 ): 685 - 692 .
Huang LY , Liu YN , Li LL , et al . Momordica charantia small extracellular vesicles mitigate neuronal ferroptosis by inhibition of GPX4 ubiquitination in ischemic stroke [J ] . Phytomedicine , 2025 , 148 : 157298 .
Lang T , Qin KY , Shao L , et al . Glycosides of Buyang Huanwu decoction alleviate cerebral infarction injury by inhibiting neuronal pyroptosis via astrocyte-derived exosomal miR-378b_L+1 [J ] . J Ethnopharmacol , 2025 , 352 : 120234 .
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