职业性矽肺生物标志物检测技术的研究进展

摘要/Abstract

摘要：

矽肺是职业性尘肺病的一种，其发病机制并不十分明确。接触性生物标志物、效应性生物标志物和易感性生物标志物可以预测矽肺的发生和评估矽肺的进展及预后。酶联免疫吸附技术和化学发光免疫反应技术、聚合酶链式反应技术、质谱技术较为成熟，但对实验室和实验设备有较高的要求。液相芯片技术、微流控技术和纳米传感器技术的“一体化”技术简化操作流程，实现快速检测，为未来研发职业病生物标志物检测技术指出了一个新的方向。同时提出了“生物标志物动态监测-多维度联合筛查-风险分层干预”的防控路径，为矽肺的早期预警、个体化干预及卫生政策优化提供新的策略。本文对职业性矽肺生物标志物检测技术的研究进展予以综述，以期为相关研究提供参考。

关键词: 矽肺, 生物标志物, 实验室检测技术, “一体化”检测技术

Abstract:

Silicosis，a type of occupational pneumoconiosis，has a pathogenesis that is not yet fully elucidated. Contact biomarkers，effect biomarkers，and susceptibility biomarkers can predict the onset of silicosis，as well as assess its progression and prognosis. Enzyme-linked immunosorbent assay（ELISA），chemiluminescence immunoassay（CLIA），polymerase chain reaction（PCR），and mass spectrometry technology are mature but require advanced laboratory facilities and equipment. "All-in-one" detection technology like liquid chip technology，microfluidic technology，and nanosensor technology simplify operational workflows and enable rapid detection，pointing to a new direction for developing occupational disease biomarker detection technologies. At the same time，the proposed prevention and control pathway of "dynamic biomarker monitoring-multi-dimensional joint screening-risk stratified intervention" offers new strategies for early warning of silicosis，personalized interventions，and optimization of public health policies. This paper provides a comprehensive review of the research progress in biomarker detection technology for occupational silicosis, aiming to serve as a reference for related studies.

Key words: Silicosis, Biomarker, Laboratory testing techniques, "All-in-one" detection technology

中图分类号:

R135.2

耿剑, 黄晓霞, 张春艳, 王庞宇, 王宪昂. 职业性矽肺生物标志物检测技术的研究进展. [J]职业与健康, 2026, 42(9): 1277-1283.

GENG Jian, HUANG Xiaoxia, ZHANG Chunyan, WANG Pangyu, WANG Xianang. Research progress on biomarker detection techniques for occupational silicosis. [J]OCCUPATION AND HEALTH, 2026, 42(9): 1277-1283.

图/表 1

参考文献 66

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项目	技术分类	技术名称	原理/方法	检测标志物/应用	样本类型	优势	局限性	技术延伸
实验室检测技术	ELISA 技术	ELISA	基于抗原-抗体反应，通过酶标抗体与底物显色进行定量分析	TNF-α、TGF-β、 CC16、KL-6、 CTGF、IL-1β等	血液、体液	操作简单、商品化程度高	特异性有限、精密度低，易受人为操作和试剂质量影响
	CLIA技术	CLIA	抗原-抗体反应结合，化学发光信号检测	TNF-α、TGF-β、 CC16、KL-6、 CTGF、IL-1β等	血液、体液	自动化程度高、可检测微量物质	设备成本较高
	PCR技术	qPCR	通过荧光探针标记核酸，实时扩增并检测基因表达量	miR-204-3P、 Fibronectin、 Vimentin、 Collagen Ⅰ/ Ⅲ等基因 mRNA	血液、组织、体液	灵敏度高、可定量分析	需严格实验条件，操作复杂
	蛋白印迹技术	Western Blot	SDS-PAGE电泳分离蛋白，转膜后通过特异性抗体检测	蛋白类	组织、细胞	灵敏度高、特异性强	操作复杂、耗时长、影响因素多	单细胞分辨率蛋白质印迹技术、毛细管和微芯片电泳、微流体自动蛋白质印迹、使用毛细血管电泳和微芯片电泳蛋白质印迹技术
	质谱技术	ICP-MS	电离样本后通过质荷比分析技术	硅元素、二氧化硅以及呼出气中生物标志物	组织、全血、呼出气	高灵敏度（酸法处理，检测限0.20 μg/g；碱法处理，检测限0.46 μg/L）	样本前处理复杂	spICP-MS、SPME-GC-MS、SELDI-TOF-MS
“一体化“检测技术	液相芯片技术	液相芯片技术	荧光编码微球结合抗原-抗体/核酸杂交反应，与荧光标记抗体结合，双激光检测	TNF-α、IL-6、 CCL2、 CXCL10等	血液、体液	样本用量少、操作简单、快速、成本低、灵活性好	仅能检测2~ 16个样本	液相芯片多重检测技术
	微流控技术	微流控芯片	微流控技术与芯片技术结合，样品处理、分析、检测和其他过程集成到芯片中	IL-13、IL-6、 MUC5AC等；气道模拟	体外模型、血液	小型化、集成化、高通量能力和耗时低	技术开发难度大，临床应用未成熟	人肺远端气道芯片模型、人类芯片上的单个肺泡模型、LOC免疫分析技术
	纳米传感器技术	SWCNT纳米传感器	至少使用一种纳米材料将生物感受器、换能器、信号处理器和显示单元集于一体的检测系统	IL-6、TNF-α以及呼出气中生物标志物	体液、呼出气	尺寸小、质量轻、消耗低和光学性质明显，检测范围25~25 000 pg/mL	需优化稳定性和特异性	石墨烯纳米传感器；16个有机纳米纤维传感器阵列以及定制的样品处理系统

项目	技术分类	技术名称	原理/方法	检测标志物/应用	样本类型	优势	局限性	技术延伸
实验室检测技术	ELISA 技术	ELISA	基于抗原-抗体反应，通过酶标抗体与底物显色进行定量分析	TNF-α、TGF-β、 CC16、KL-6、 CTGF、IL-1β等	血液、体液	操作简单、商品化程度高	特异性有限、精密度低，易受人为操作和试剂质量影响
	CLIA技术	CLIA	抗原-抗体反应结合，化学发光信号检测	TNF-α、TGF-β、 CC16、KL-6、 CTGF、IL-1β等	血液、体液	自动化程度高、可检测微量物质	设备成本较高
	PCR技术	qPCR	通过荧光探针标记核酸，实时扩增并检测基因表达量	miR-204-3P、 Fibronectin、 Vimentin、 Collagen Ⅰ/ Ⅲ等基因 mRNA	血液、组织、体液	灵敏度高、可定量分析	需严格实验条件，操作复杂
	蛋白印迹技术	Western Blot	SDS-PAGE电泳分离蛋白，转膜后通过特异性抗体检测	蛋白类	组织、细胞	灵敏度高、特异性强	操作复杂、耗时长、影响因素多	单细胞分辨率蛋白质印迹技术、毛细管和微芯片电泳、微流体自动蛋白质印迹、使用毛细血管电泳和微芯片电泳蛋白质印迹技术
	质谱技术	ICP-MS	电离样本后通过质荷比分析技术	硅元素、二氧化硅以及呼出气中生物标志物	组织、全血、呼出气	高灵敏度（酸法处理，检测限0.20 μg/g；碱法处理，检测限0.46 μg/L）	样本前处理复杂	spICP-MS、SPME-GC-MS、SELDI-TOF-MS
“一体化“检测技术	液相芯片技术	液相芯片技术	荧光编码微球结合抗原-抗体/核酸杂交反应，与荧光标记抗体结合，双激光检测	TNF-α、IL-6、 CCL2、 CXCL10等	血液、体液	样本用量少、操作简单、快速、成本低、灵活性好	仅能检测2~ 16个样本	液相芯片多重检测技术
	微流控技术	微流控芯片	微流控技术与芯片技术结合，样品处理、分析、检测和其他过程集成到芯片中	IL-13、IL-6、 MUC5AC等；气道模拟	体外模型、血液	小型化、集成化、高通量能力和耗时低	技术开发难度大，临床应用未成熟	人肺远端气道芯片模型、人类芯片上的单个肺泡模型、LOC免疫分析技术
	纳米传感器技术	SWCNT纳米传感器	至少使用一种纳米材料将生物感受器、换能器、信号处理器和显示单元集于一体的检测系统	IL-6、TNF-α以及呼出气中生物标志物	体液、呼出气	尺寸小、质量轻、消耗低和光学性质明显，检测范围25~25 000 pg/mL	需优化稳定性和特异性	石墨烯纳米传感器；16个有机纳米纤维传感器阵列以及定制的样品处理系统