中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (19): 5000-5006.doi: 10.12307/2026.144

• 干细胞综述 stem cell review • 上一篇    下一篇

外泌体miRNA作为脑小血管病早期诊断的生物标志物和潜在治疗靶点

刘雨旋1，关东升2，王  靖1，任翼菡1   

  1. 1河南中医药大学第二临床医学院，河南省郑州市   450046；2河南省中医院，河南省郑州市   450002
  • 收稿日期:2025-06-16 接受日期:2025-08-05 出版日期:2026-07-08 发布日期:2026-02-24
  • 通讯作者: 关东升，教授，主任医师，博士研究生导师，河南省中医院，河南省郑州市 450002
  • 作者简介:刘雨旋，女，1999年生，湖北省黄石市人，汉族，硕士，主要从事中医药防治脑病方面的研究。
  • 基金资助:
    国家自然科学基金项目(81673943)，项目负责人：关东升；全国中医药创新骨干人才培训项目[国中医药人教函(2019)128号]，项目
    参与人：关东升；河南省重点研发与推广专项(科技攻关)(242102310564)，项目负责人：关东升；河南省重点研发与推广专项(科技攻关)(232102310444)，项目负责人：关东升；河南省高等学校重点科研项目(23A360021)，项目负责人：关东升

Exosomal miRNA as an early diagnostic biomarker and potential therapeutic target for cerebral small vessel disease

Liu Yuxuan1, Guan Dongsheng2, Wang Jing1, Ren Yihan1   

  1. 1Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; 2Henan Province Hospital of TCM, Zhengzhou 450002, Henan Province, China
  • Received:2025-06-16 Accepted:2025-08-05 Online:2026-07-08 Published:2026-02-24
  • Contact: Guan Dongsheng, Professor, Chief physician, Doctoral supervisor, Henan Province Hospital of TCM, Zhengzhou 450002, Henan Province, China
  • About author:Liu Yuxuan, MS, Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81673943 (to GDS); National Training Project for Innovative Key Talents in Traditional Chinese Medicine, No. (2019)128 (to GDS); Henan Province Key R&D and Promotion Project (Science and Technology Research), No. 242102310564 (to GDS); Henan Province Key R&D and Promotion Project (Science and Technology Research), No. 232102310444 (to GDS); Henan Province Key Scientific Research Project of Higher Education Institutions, No. 23A360021 (to GDS) 

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摘要：

文题释义：

脑小血管病：是指由于各种病因影响脑内小动脉、微动脉、毛细血管、微静脉和小静脉所导致的一系列临床、影像、病理综合征，主要表现为腔隙性脑梗死、脑出血、皮质下白质病变、脑微出血和微梗死。
microRNA：是由来源于细胞核中的18-25个核苷酸组成的单链非编码RNA小分子，由受体细胞释放，通过转录或切割靶向信使RNA特异性结合以调控多个靶基因表达，同时参与调节多种细胞和分子途径。

摘要
背景：近年来，miRNA在脑小血管病的发病机制和诊疗手段中受到广泛关注，其参与调控脑小血管病的多种病理过程。 
目的：综述miRNA在脑小血管病发病机制、诊断、治疗中的作用，为脑小血管病的早期诊断提供新型潜在生物学标志物和有效治疗靶点。
方法：以“micro RNA，cerebral small vessel disease，blood-brain barrier，chronic cerebral hypoperfusion，inflammation， apoptosis，diagnosis，biomarkers”为英文检索词和“外泌体miRNA，脑小血管病”为中文检索词，分别检索PubMed及中国知网，检索时限为各数据库建库至2025年1月。通过阅读文题及摘要进行初步筛选，排除研究内容相关性差及内容重复的文献，最终纳入72篇文献进行归纳总结。

结果与结论：①通过对外泌体miRNA的生物学功能及特性进行挖掘探讨，证实外泌体miRNA是脑小血管病发生发展过程中的重要相关成分；②外泌体miRNA参与调控脑小血管病的多种病理过程，通过保护血脑屏障、改善慢性脑灌注不足、减轻炎症反应、抑制细胞凋亡等多个方面，在脑小血管病病理机制中发挥重要作用；③外泌体miRNA通过靶向多个信号通路在病理机制的不同发展阶段进行干预，可以有效针对脑小血管病的不同病理环节；④多种外泌体miRNA联合使用可以有效改善脑小血管病进程，不同miRNA的调控作用在病理机制的各个阶段发挥不同作用，构建miRNA作用网络对于调控脑小血管病发展具有重要意义；⑤外泌体miRNA广泛稳定存在于各种体液中，其在脑小血管病患者尿液、血清、血液等体液中的特异性与显著性表达可作为脑小血管病患者诊断的有效依据；⑥目前临床主要治疗手段为注射miRNA模拟物或拮抗剂调节下游靶基因的表达，如何发挥miRNA最有效的治疗效果仍需深入研究；⑦miRNA作为外泌体内容物在治疗脑小血管病中具有极大的应用前景，未来应进一步深入挖掘其作用机制，为临床治疗脑小血管病方案提供有效思路并进一步优化。

https://orcid.org/0009-0002-3927-2743 (刘雨旋) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 外泌体, miRNA, 脑小血管病, 血脑屏障, 慢性脑灌注不足, 炎症, 细胞凋亡, 生物学标志物

Abstract: BACKGROUND: In recent years, microRNA (miRNA) has received extensive attention in the pathogenesis and diagnosis and treatment of cerebral small vessel disease, and is involved in the regulation of various pathological processes of cerebral small vessel disease.
OBJECTIVE: To review the role of miRNA in the pathogenesis, diagnosis, and treatment of cerebral small vessel disease, and to provide effective therapeutic targets and new potential biomarkers for the early diagnosis of cerebral small vessel disease.
METHODS: “microRNA, cerebral small vessel disease, blood-brain barrier, chronic cerebral hypoperfusion, inflammation, apoptosis, diagnosis, biomarkers” were used as English search terms for PubMed search. “Exosomal miRNA, cerebral small vessel disease” were used as Chinese search terms for CNKI search. The search time limit was from inception to January 2025. Through the preliminary screening of reading titles and abstracts, the literature with poor relevance and duplicate content was excluded, and finally 72 articles were included for inductive discussion.
RESULTS AND CONCLUSION: (1) Through the excavation and discussion of the biological functions and characteristics of exosomal miRNAs, it was confirmed that exosomal miRNAs are important related components in the occurrence and progression of cerebral small vessel disease diseases. (2) Exosomal miRNA participates in the regulation of various pathological processes of cerebral small vessel disease, and plays an important role in the pathological mechanism of cerebral small vessel disease by protecting the blood-brain barrier, improving chronic cerebral hypoperfusion, reducing inflammatory response, and inhibiting apoptosis. (3) Exosomal miRNA can effectively target different pathological links of cerebral small vessel disease by targeting multiple signaling pathways to intervene at different stages of pathological development. (4) The combination of multiple exosomal miRNAs can effectively improve the disease process of cerebral small vessel disease, and the regulatory effects of different miRNAs play different roles in each stage of the pathological mechanism, and the construction of miRNA action network is of great significance for regulating the development of cerebral small vessel disease. (5) Exosomal miRNAs are widely and stably present in various body fluids, and their specific and significant expression in urine, serum, blood and other body fluids of cerebral small vessel disease patients can be used as an effective basis for the diagnosis of cerebral small vessel disease patients. (6) At present, the main clinical treatment method is to inject miRNA mimics or antagonists to regulate the expression of downstream target genes, and how to exert the most effective therapeutic effect of miRNA still needs to be further studied. (7) As exosome contents, miRNA has great application prospects in the treatment of cerebral small vessel disease. In the future, its mechanism of action should be further explored to provide effective ideas and further optimize the clinical treatment of cerebral small vessel disease.


Key words: exosome, miRNA, cerebral small vessel disease, blood-brain barrier, chronic cerebral hypoperfusion, inflammation, apoptosis, biological marker

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