类风湿关节炎患者血浆外泌体下调miRNA的 差异表达及其临床诊断价值研究
Differential Expression of Downregulated miRNAs in Plasma Exosomes of Rheumatoid Arthritis Patients and Their Clinical Diagnostic Value
DOI: 10.12677/acm.2026.1641441, PDF,   
作者: 唐凌霄, 帅宗文*：安徽医科大学第一附属医院风湿病与免疫科，安徽 合肥
关键词: 类风湿性关节炎；微小RNA；外泌体；生物标志物；Rheumatoid Arthritis； microRNA； Exosomes； Biomarkers
摘要: 目的：探讨类风湿关节炎(RA)患者血浆外泌体中miR-200a-3p、miR-133a-3p、miR-3960及miR-184-3p的表达水平及其在RA早期诊断和病情活动度监测中的临床意义。方法：选取2023年1月至2024年12月于安徽医科大学第一附属医院就诊的30例RA患者(活动组20例，稳定组10例)及20例健康对照(HC)。采用超速离心法及试剂盒法提取血浆外泌体，并通过透射电镜(TEM)、纳米粒径分析及标志蛋白(CD9、CD81)进行鉴定。利用高通量测序筛选差异miRNAs，并应用qRT-PCR对候选下调miRNAs进行扩大样本验证。分析各miRNA表达水平与临床指标(DAS28-CRP、CRP等)的相关性，并采用ROC曲线评价其诊断效能。结果：成功分离并鉴定出符合特征的血浆外泌体。qRT-PCR结果显示，RA患者血浆外泌体中miR-200a-3p、miR-133a-3p、miR-3960及miR-184-3p的表达水平均显著低于HC组(均P < 0.001)。其中，miR-200a-3p、miR-133a-3p、miR-184-3p在活动期RA组中的表达显著低于稳定组(均P < 0.01)，且与DAS28-CRP及CRP呈负相关。ROC曲线显示，miR-200a-3p、miR-133a-3p、miR-184-3p三者联合诊断的AUC为0.921，灵敏度86.0%，特异度88.0%。结论：RA患者血浆外泌体中存在显著下调的miRNA谱，miR-200a-3p、miR-133a-3p和miR-184-3p可作为评估RA疾病诊断及病情活动性的潜在无创生物标志物。
Abstract: Objective: To investigate the expression levels of miR-200a-3p, miR-133a-3p, miR-3960, and miR-184-3p in plasma exosomes of rheumatoid arthritis (RA) patients and their clinical significance in early diagnosis and disease activity monitoring. Methods: A total of 30 RA patients (20 in the active group and 10 in the stable group) and 20 healthy controls (HC) were selected from the First Affiliated Hospital of Anhui Medical University between January 2023 and December 2024. Plasma exosomes were isolated using ultracentrifugation and reagent kits, and characterized by transmission electron microscopy (TEM), nanoparticle size analysis, and marker proteins (CD9, CD81). High-throughput sequencing was performed to identify differential miRNAs, and qRT-PCR was used to validate the expression of candidate downregulated miRNAs in an expanded sample. The correlation between miRNA expression levels and clinical parameters (DAS28-CRP, CRP, etc.) was analyzed, and ROC curves were used to assess their diagnostic efficiency. Results: Plasma exosomes with characteristic features were successfully isolated and identified. qRT-PCR results showed that the expression levels of miR-200a-3p, miR-133a-3p, miR-3960, and miR-184-3p in plasma exosomes of RA patients were significantly lower than those of the HC group (all P < 0.001). Among them, miR-200a-3p, miR-133a-3p, and miR-184-3p were significantly lower in the active RA group compared to the stable group (all P < 0.01), and were negatively correlated with DAS28-CRP and CRP. ROC analysis showed that the combined diagnostic AUC of miR-200a-3p, miR-133a-3p, and miR-184-3p was 0.921, with a sensitivity of 86.0% and a specificity of 88.0%. Conclusion: A significantly downregulated miRNA profile exists in plasma exosomes of RA patients. miR-200a-3p, miR-133a-3p, and miR-184-3p could serve as potential non-invasive biomarkers for evaluating RA diagnosis and disease activity.
文章引用：唐凌霄, 帅宗文. 类风湿关节炎患者血浆外泌体下调miRNA的 差异表达及其临床诊断价值研究[J]. 临床医学进展, 2026, 16(4): 1981-1990. https://doi.org/10.12677/acm.2026.1641441

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