细胞外囊泡与结核病诊断的研究进展

doi:10.19982/j.issn.1000-6621.20250091

摘要/Abstract

摘要：

结核病的诊断仍然是公共卫生领域的一大难题,利用细胞外囊泡(extracellular vesicle,EV)诊断结核病是目前的研究热点。EV是纳米级膜状结构,在宿主-微生物相互作用的细胞内和细胞间通讯中至关重要,其携带的微生物特异性抗原物质对于疾病的诊断具有巨大潜力。寻找EV新型生物标志物、利用高敏感核酸技术或使用纳米材料富集结核病患者体液中EV是提高结核病诊断准确性的主要研究方向。笔者介绍了EV及其中重要生物标志物在肺结核及肺外结核方面的诊断潜力和研究进展,阐述了EV在结核病诊断中的技术瓶颈与突破方向,为跨学科研究提供理论框架。

关键词: 外泌体, 结核, 生物学标记, 诊断, 鉴别

Abstract:

The early and accurate diagnosis of tuberculosis (TB) remains a pressing challenge in global public health. In recent years, extracellular vesicle (EV) have emerged as a promising avenue for TB diagnostics. EV are nanoscale, membrane-bound structures that play critical roles in both intracellular and intercellular communication during host-pathogen interactions. Notably, they encapsulate microbial antigenic components with high specificity, offering considerable potential as novel biomarkers for disease detection. Current research efforts focus on identifying novel EV-derived biomarkers, applying highly sensitive nucleic acid detection technologies, and employing nanomaterial-based enrichment strategies to enhance the diagnostic yield of EV in the body fluids of patients with TB. This review summarizes the diagnostic value and recent advances in EV and their associated biomarkers in both pulmonary TB and extrapulmonary TB. Key technical limitations and potential breakthroughs are discussed, aiming to establish a conceptual framework that may guide future interdisciplinary investigations in this rapidly evolving field.

Key words: Exosomes, Tuberculosis, Biological markers, Diagnosis, differential

中图分类号:

朱清玉, 刘家云, 龙铟. 细胞外囊泡与结核病诊断的研究进展[J]. 中国防痨杂志, 2025, 47(8): 1077-1084. doi: 10.19982/j.issn.1000-6621.20250091

Zhu Qingyu, Liu Jiayun, Long Yin. Advances in the application of extracellular vesicles and the diagnosis of tuberculosis[J]. Chinese Journal of Antituberculosis, 2025, 47(8): 1077-1084. doi: 10.19982/j.issn.1000-6621.20250091

图/表 2

图1

表1

外泌体非编码RNA在诊断结核病中的研究进展

研究对象	标本类型	ncRNA检测	ncRNA	研究结果	参考文献
结核病与健康人	血浆外泌体	高通量测序、 RT-qPCR	miR-185-5p	在结核病患者血浆外泌体中的水平显著升高	Kaushik 等^[36]
结核病与健康人	血浆外泌体	生物信息学、 RT-qPCR	miR-26a-5p、miR-151a-3p	结核病患者血浆外泌体来源miR-26a-5p表达水平降低,miR151a-3p表达水平升高	冯真等^[37]
活动性结核病和健康人	血浆外泌体	GEO数据集和 NONCODE数据库的综合分析	NONHSAT101518.2、 NONHSAT067134.2、 NONHSAT148822.1、 NONHSAT078957.2	4种lncRNA明显下调	Fang等^[38]
活动性结核病和健康人	血浆外泌体	Small-RNA 转录组分析	miR-766-3p、miR-1283、 miR-125a-5p、miR-376c-3p	可能作为结核病诊断的候选标志	Cui等^[39]
结核病、LTBI与健康人	血清外泌体	Small RNA-seq	hsa-let-7e-5p、hsa-let-7d-5p、 hsa-miR-450a-5p、hsa-miR-140-5p;hsa-miR-1246、hsa-miR-2110、 hsa-miR-370-3P、hsa-miR-28-3p、hsa-miR-193b-5p	特异性表达	Lyu等^[40]
活动性结核病、LTBI与健康人	血清外泌体	高通量测序、 RT-qPCR	3个tRFs(tRF-56:75-Trp-CCA-4、tRF-1:22-chrM.Ser-GCT、 tRF-56:76Val-TAC-1-M2)	活动性结核病患者和LTBI中tRFs表达水平存在差异	Xi等^[41]
活动性结核病、LTBI和健康人	血清外泌体	RT-qPCR	miR-27a	表达上调	郑甜等^[42]
LTBI与健康人	血浆外泌体	Small RNA-seq	hsa-miR-7850-5p、hsa-miR-1306-5p、 hsa-miR-363-5p、hsa-miR-374a-5p、 hsa-miR-4654、has-miR-6529-5p、 hsa-miR-140-5p	在LTBI个体中特异性表达升高	Cui等^[43]
MDR-TB与健康人	血清EV	qPCR	miR-let7e-5p	在MDR-TB中观察到miR-let-7e-5p上调	Carranza 等^[44]
MDR-TB	血浆外泌体	RT-qPCR	miR-346	血浆外泌体miR-346高表达与MDR-TB治疗结果不良高风险有关,有希望作为MDR-TB治疗结局预测的有用标志物	胡萍等^[45]
结核病、TBM和健康人	血浆外泌体	微阵列分析、 qRT-PCR	miR-20a、miR-20b、miR-26a、 miR-106a、miR-191、miR-486	在结核病患者中存在差异表达	Hu等^[46]
HIV感染合并结核病患者与HIV感染	血浆外泌体	RT-qPCR	miR-20a、miR-20b、miR-26a、 miR-106a、miR-191、miR-486	表达升高	Jin等^[47]

表1

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