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目的 探讨犬尿氨酸-3-单加氧酶（KMO）对类风湿关节炎（RA）成纤维样滑膜细胞（FLS）功能的影响。方法 通过生物信息学分析RA和健康对照（HC）组滑膜组织KMO表达；收集RA患者和HC滑膜组织，免疫荧光（IF）检测滑膜组织FLS中KMO表达情况；体外利用人类风湿关节炎成纤维样滑膜细胞（MH7A），对MH7A进行过表达、敲低及KMO特异性抑制剂Ro61-8048抑制KMO后，通过Western blot、CCK-8、EdU、Transwell和ELISA等方法检测MH7A细胞活力、增殖、迁移及分泌功能的变化。结果 生物信息学分析表明，RA滑膜组织KMO基因表达显著高于HC组（P<0.001）;IF结果显示，与HC组相比，RA滑膜组织FLS中KMO表达增加（P<0.01）；过表达KMO后，MH7A细胞活力、增殖、迁移和分泌能力增强（均P<0.05）;MH7A细胞敲低和Ro61-8048抑制KMO后，显著抑制MH7A细胞活力、增殖、迁移和分泌能力（均P<0.05）。结论 KMO在RA滑膜组织中表达上调，并促进RA-FLS活化，可能是RA治疗的潜在靶点。
Abstract：Objective To investigate the effect of kynurenine-3-monooxygenase(KMO) on the function of fibroblast-like synoviocytes(FLS) in rheumatoid arthritis(RA).Methods KMO expression in synovial tissues from RA patients and healthy controls(HC) was analyzed using bioinformatics. Synovial tissues from RA patients and HC were collected, and KMO expression in FLS within synovial tissues was detected by immunofluorescence(IF). In vitro experiments were performed using human rheumatoid arthritis fibroblast-like synoviocytes(MH7A). Following KMO overexpression, KMO knockdown, and KMO inhibition with the specific inhibitor Ro61-8048 in MH7A cells, Western blot, CCK-8, EdU, Transwell and ELISA assays were used to evaluate alterations in cell viability, proliferation, migration and secretory function.Results Bioinformatic analysis revealed significantly higher KMO gene expression in RA synovial tissue compared to the HC group(P<0. 001). IF results showed increased KMO expression in FLS from RA synovial tissues relative to the HC group(P<0. 01). Overexpression of KMO led to enhanced viability, proliferation, migration, and secretory capabilities of MH7A cells(all P<0. 05), whereas knockdown or inhibition of KMO with Ro61-8048 markedly suppressed these functions(all P<0. 05).Conclusion The expression of KMO is upregulated in the synovial tissues of RA patients and promotes the activation of RA-FLS, suggesting that KMO may serve as a potential therapeutic target for RA treatment.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.08.010
中图分类号:R593.22
引用信息:
[1]贾永平,宗雪梅,汪艳楠,等.犬尿氨酸-3-单加氧酶对类风湿关节炎成纤维样滑膜细胞功能的影响[J].安徽医科大学学报,2026(08):1408-1415.DOI:10.19405/j.cnki.issn1000-1492.2026.08.010.
基金信息:
国家自然科学基金项目(编号:82430114); 安徽省自然科学基金项目(编号:2108085MH320); 安徽省高校科研基金项目(编号:2024AH050745); 安徽省转化医学研究院科研基金项目(编号:2023zhyx-C11); 重大疾病新药靶发现及新药创制全国重点实验室开放课题(编号:SKLD2025M11); 安徽省优秀科研创新团队项目(编号:2024AH010013); 安徽医科大学科研机构建设提升计划资助项目(编号:2025xkjT013)
2026-07-20
2026-07-20
2026-07-20