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红细胞来源细胞外囊泡的生理功能及临床应用研究进展

潘宏宇¹, 程思雨², 王竟苇¹, 林乐萱¹, 李鑫雨¹, 高程杰¹, 石莉红^1,3,*

¹中国医学科学院血液病医院(中国医学科学院血液学研究所)，血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020；²天津医科大学，细胞生态海河实验室，天津 300070；³天津医学健康研究院，天津 301600

摘要

红细胞来源细胞外囊泡(red blood cell-derived extracellular vesicles, RBC-EVs)是血液中含量丰富的细胞外囊泡之一，在细胞间通讯、疾病发展及医学应用中具有关键作用。RBC-EVs的结构与红细胞存在差异，囊泡膜呈现磷脂酰丝氨酸外翻、膜蛋白减少等特征，包含血红蛋白、miRNA等活性分子。RBC-EVs主要以微囊泡和外泌体的形式存在，分别通过细胞膜出芽和多囊泡体途径产生，体内清除主要依赖肝脏库普弗细胞(Kupffer cells)的吞噬作用。生理功能上，RBC-EVs可通过去除红细胞膜上的损伤、衰老信号来维持红细胞的正常生理功能，参与一氧化氮平衡与抗凝血过程来进行生物体的稳态调节，还能参与免疫调控并发挥一定的抗病毒作用等，同时可作为细胞间信息载体在不同疾病中发挥功能。凭借其高生物相容性、低免疫原性等优势，RBC-EVs作为小分子药物如核酸的载体，在血液系统疾病、肝病、癌症等领域展现出巨大的临床应用前景。本文系统综述了RBC-EVs的组成与结构、生成与清除机制、主要生理功能、临床应用与未来展望。

关键词： 红细胞; 细胞外囊泡; 促凝与抗凝; 免疫调节; 微载体

Progress on the physiological functions and clinical applications of red blood cellderived extracellular vesicles

PAN Hong-Yu¹, CHENG Si-Yu², WANG Jing-Wei¹, LIN Le-Xuan¹, LI Xin-Yu¹, GAO Cheng-Jie¹, SHI Li-Hong^1,3,*

¹State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China；²Tianjin Medical University, Haihe Laboratory of Cell Ecosystem, Tianjin 300070, China；³Tianjin Institutes of Health Science, Tianjin 301600, China

Abstract

Red blood cell-derived extracellular vesicles (RBC-EVs) are one of the most abundant types of extracellular vesicles (EVs) in the blood, playing a crucial role in intercellular communication, disease progression, and medical applications. The structure of RBC-EVs differs from that of red blood cells (RBCs), characterized by phosphatidylserine externalization, reduced membrane proteins, and encapsulation of bioactive molecules such as hemoglobin and miRNAs. RBC-EVs primarily exist as microvesicles and exosomes, which are generated through membrane budding and the multivesicular bodies pathway, respectively. Their clearance in vivo mainly relies on phagocytosis by hepatic Kupffer cells. Physiologically, RBC-EVs maintain the normal physiological functions of RBCs by removing damaged and senescent signals from the RBC membrane, regulate organismal homeostasis through participation in nitric oxide balance and anticoagulant processes, and also engage in immune regulation and exert certain antiviral effects. Additionally, they serve as intercellular information carriers to function in various diseases. Endowed with advantages such as high biocompatibility and low immunogenicity, RBC-EVs have demonstrated enormous clinical application potential as carriers for small-molecule drugs (e.g., nucleic acids) in fields including hematological diseases, liver diseases, and cancer. This review systematically summarizes the composition and structure, biogenesis and clearance mechanisms, main physiological functions, clinical applications, and future prospects of RBC-EVs.

Key words: red blood cell; extracellular vesicles; procoagulation and anticoagulation; immunomodulation; microcarrier

收稿日期：　　录用日期：

通讯作者：石莉红　　E-mail:

DOI: 10.13294/j.aps.2026.0068

引用本文：

潘宏宇, 程思雨, 王竟苇, 林乐萱, 李鑫雨, 高程杰, 石莉红. 红细胞来源细胞外囊泡的生理功能及临床应用研究进展[J]. 生理学报 2026; 78 (4): 789-802.

PAN Hong-Yu, CHENG Si-Yu, WANG Jing-Wei, LIN Le-Xuan, LI Xin-Yu, GAO Cheng-Jie, SHI Li-Hong. Progress on the physiological functions and clinical applications of red blood cellderived extracellular vesicles. Acta Physiol Sin 2026; 78 (4): 789-802 (in Chinese with English abstract).