精神分裂症外泌体源性生物标志物的研究进展

doi:10.3969/j.issn.1673-8640.2026.10.014

摘要/Abstract

摘要：

精神分裂症（SCZ）的临床诊断目前高度依赖症状学评估，亟需稳定、可靠的生物标志物来实现SCZ的早期识别和精准治疗。外泌体及其携带的核酸、蛋白质、脂质等生物活性分子在疾病的发生、发展中具有重要作用，目前已成为研究的热点。SCZ患者外泌体及其相关成分呈现出特异性改变，与SCZ的病理、生理机制密切相关，这使其成为极具潜力的SCZ生物标志物。文章对外泌体非编码RNA、蛋白质、脂质等分子作为SCZ潜在诊断标志物的研究进展进行综述，为SCZ新型诊断工具的研发提供新的理论依据和研究方向。

关键词: 外泌体, 非编码RNA, 精神分裂症, 生物标志物

Abstract:

The current clinical diagnosis of schizophrenia（SCZ） relies on symptom assessment. There is an urgent need for stable and reliable biomarkers to achieve early identification and precise treatment of SCZ. Exosomes and biological active molecules，such as nucleic acids，proteins and lipids，play roles in the occurrence and development of SCZ，making them a research hotspot. The exosomes and their related components of SCZ patients show specific changes，which are related to the pathophysiological mechanism of SCZ，making them a potential biomarker for SCZ. This review focuses on the research progress of exosome non-coding RNA，proteins，lipids and so on，as potential diagnostic markers for SCZ，providing new theoretical basis and research directions for the development of new diagnostic tools for SCZ.

Key words: Exosome, Non-coding RNA, Schizophrenia, Biomarker

中图分类号:

R446.1

符小妹, 金伟峰, 李丹, 陈姝子, 李振华, 马佩俊, 林萍. 精神分裂症外泌体源性生物标志物的研究进展[J]. 检验医学, 2026, 41(10): 1022-1029.

FU Xiaomei, JIN Weifeng, LI Dan, CHEN Shuzi, LI Zhenhua, MA Peijun, LIN Ping. Research progress on exosome-derived biomarkers of schizophrenia[J]. Laboratory Medicine, 2026, 41(10): 1022-1029.

图/表 2

参考文献 38

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名称	表达变化	样本来源	检测方法	研究对象	可能涉及的机制	参考文献
ncRNA
miR-497	上调	脑组织^①	qPCR^②	SCZ患者8例、健康对照者13名	未提及	[10]
miR-223	上调	脑眶额叶皮质^①	RT-qPCR	SCZ患者29例、健康对照者25名	谷氨酸受体功能减退，神经炎症	[11]
miR-206	上调	血清	RT-qPCR	训练集：23/23 测试集：23/23 技术验证：SCZ患者100、健康对照者 100名	调节BDNF	[12]
miR-675	上调	血浆	qPCR	SCZ患者9例、健康对照者9名	MEF2C功能缺陷，神经炎症	[14]
miR-137	上调	血浆	RT-qPCR	SCZ患者138例、健康对照者134名	氧化应激	[15]
chr3_196488683_ 196483770_-4913等	上调	血浆	RT-qPCR	发现队列：SCZ患者5例、健康对照者5名验证队列：SCZ患者6例、健康对6名	DNA损伤，组蛋白泛素化，应激反应	[17]
chr15：93496587-93499879+ -hsa-miR-20b-5p-ANK网络等	未提及	血浆	RT-qPCR	发现队列：SCZ患者10例、健康对照者 10名验证队列：SCZ患者31例、健康对照者 31名	神经发育，突触功能	[18]
MIAT、PVT1	未提及	血清	RT-qPCR	SCZ患者56例、健康对照者96名	未提及	[20]
ENSG00000251562-miR-26a-5p-EZH2网络	未提及	血浆	高通量测序	SCZ患者10例、健康对照者10名	中枢神经系统增殖和分化调控	[21]
ENSG00000251562-miR-22-3p-SIRT1网络	未提及	血浆	高通量测序	SCZ患者10例、健康对照者10名	多巴胺能信号通路	[21]
蛋白
MFN2、CYPD、humanin、MOTS-c	下调	血浆、ADEV和NDEV	ELISA^③	SCZ患者10例、健康对照者10名	线粒体功能障碍、神经元损伤和代谢紊乱	[23]
SNPH	上调		ELISA	SCZ患者10例、健康对照者10名	线粒体功能异常	[23]
LETM1、TRPM4、NCLX	下调	血浆、NDEV	ELISA	SCZ患者10例、健康对照者10名	线粒体钙离子调控网络异常	[24]
CACNA-1C	上调		ELISA	SCZ患者10例、健康对照者10名	线粒体钙离子调控网络异常	[24]
C3、C4、C4PBA、PROS1	上调	血浆	ELISA	SCZ患者100例、健康对照者149名	补体系统异常	[25]
P-T181-Tau蛋白、 Aβ42	上调	血浆、ADE	ELISA	SCZ患者60例、健康对照者60名	氧化应激	[26]
HSP90AA1、PSMB1、PSMB2	上调	血浆	蛋白质组学	SCZ患者15例、健康对照者45名	神经炎症，泛素-蛋白酶体通路异常	[28]
GFAP	上调	血浆	免疫印迹法	SCZ患者24例、健康对照者12名	神经炎症	[29]
α-II血影蛋白	下调	血浆	免疫印迹法	SCZ患者24例、健康对照者12名	神经元异常	[29]
FN1、ITGB3、PECAM1、ITGA6、CD5	上调/下调	血浆	高通量单外泌体表面蛋白分析	SCZ患者50例、健康对照者10名	内皮功能障碍，神经发育异常等	[30]
脂质及代谢物
Cer（d18：0/24：1）等	上调/下调	血清	超高效液相色谱-串联质谱	SCZ患者20例、健康对照者20名	脂质代谢	[35]
L-精氨酸等	上调/下调	血清	超高效液相色谱-串联质谱	训练集：SCZ患者79例、健康对照者66名； 3个测试集：SCZ患者107例、健康对照者62名；SCZ患者104例、健康对照者142名；SCZ患者96例、健康对照者62名	甘油磷脂代谢	[34]

名称	表达变化	样本来源	检测方法	研究对象	可能涉及的机制	参考文献
ncRNA
miR-497	上调	脑组织^①	qPCR^②	SCZ患者8例、健康对照者13名	未提及	[10]
miR-223	上调	脑眶额叶皮质^①	RT-qPCR	SCZ患者29例、健康对照者25名	谷氨酸受体功能减退，神经炎症	[11]
miR-206	上调	血清	RT-qPCR	训练集：23/23 测试集：23/23 技术验证：SCZ患者100、健康对照者 100名	调节BDNF	[12]
miR-675	上调	血浆	qPCR	SCZ患者9例、健康对照者9名	MEF2C功能缺陷，神经炎症	[14]
miR-137	上调	血浆	RT-qPCR	SCZ患者138例、健康对照者134名	氧化应激	[15]
chr3_196488683_ 196483770_-4913等	上调	血浆	RT-qPCR	发现队列：SCZ患者5例、健康对照者5名验证队列：SCZ患者6例、健康对6名	DNA损伤，组蛋白泛素化，应激反应	[17]
chr15：93496587-93499879+ -hsa-miR-20b-5p-ANK网络等	未提及	血浆	RT-qPCR	发现队列：SCZ患者10例、健康对照者 10名验证队列：SCZ患者31例、健康对照者 31名	神经发育，突触功能	[18]
MIAT、PVT1	未提及	血清	RT-qPCR	SCZ患者56例、健康对照者96名	未提及	[20]
ENSG00000251562-miR-26a-5p-EZH2网络	未提及	血浆	高通量测序	SCZ患者10例、健康对照者10名	中枢神经系统增殖和分化调控	[21]
ENSG00000251562-miR-22-3p-SIRT1网络	未提及	血浆	高通量测序	SCZ患者10例、健康对照者10名	多巴胺能信号通路	[21]
蛋白
MFN2、CYPD、humanin、MOTS-c	下调	血浆、ADEV和NDEV	ELISA^③	SCZ患者10例、健康对照者10名	线粒体功能障碍、神经元损伤和代谢紊乱	[23]
SNPH	上调		ELISA	SCZ患者10例、健康对照者10名	线粒体功能异常	[23]
LETM1、TRPM4、NCLX	下调	血浆、NDEV	ELISA	SCZ患者10例、健康对照者10名	线粒体钙离子调控网络异常	[24]
CACNA-1C	上调		ELISA	SCZ患者10例、健康对照者10名	线粒体钙离子调控网络异常	[24]
C3、C4、C4PBA、PROS1	上调	血浆	ELISA	SCZ患者100例、健康对照者149名	补体系统异常	[25]
P-T181-Tau蛋白、 Aβ42	上调	血浆、ADE	ELISA	SCZ患者60例、健康对照者60名	氧化应激	[26]
HSP90AA1、PSMB1、PSMB2	上调	血浆	蛋白质组学	SCZ患者15例、健康对照者45名	神经炎症，泛素-蛋白酶体通路异常	[28]
GFAP	上调	血浆	免疫印迹法	SCZ患者24例、健康对照者12名	神经炎症	[29]
α-II血影蛋白	下调	血浆	免疫印迹法	SCZ患者24例、健康对照者12名	神经元异常	[29]
FN1、ITGB3、PECAM1、ITGA6、CD5	上调/下调	血浆	高通量单外泌体表面蛋白分析	SCZ患者50例、健康对照者10名	内皮功能障碍，神经发育异常等	[30]
脂质及代谢物
Cer（d18：0/24：1）等	上调/下调	血清	超高效液相色谱-串联质谱	SCZ患者20例、健康对照者20名	脂质代谢	[35]
L-精氨酸等	上调/下调	血清	超高效液相色谱-串联质谱	训练集：SCZ患者79例、健康对照者66名； 3个测试集：SCZ患者107例、健康对照者62名；SCZ患者104例、健康对照者142名；SCZ患者96例、健康对照者62名	甘油磷脂代谢	[34]