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犬尿氨酸-3-单加氧酶在类风湿关节炎患者外周血单个核细胞和滑膜组织中的表达及意义

Expression and significance of kynurenine-3-monooxygenase in peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis
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摘要 目的探讨犬尿氨酸-3-单加氧酶(KMO)在类风湿关节炎(RA)患者外周血单个核细胞(PBMC)、滑膜组织和成纤维样滑膜细胞(FLS)中的表达及临床意义。方法收集25例健康对照(HC)个体和25例确诊为RA患者的外周血样本,采用实时荧光定量PCR和Western blot法对RA组和HC组PBMC中KMO基因和蛋白表达进行检测,并分析RA患者PBMC中KMO基因表达水平与实验室检测指标之间的相关性。同时,利用免疫组化和免疫荧光技术检测RA组和HC组滑膜组织及FLS中KMO的表达情况。结果(1)RA组PBMC中KMO基因和蛋白表达高于HC组,差异有统计学意义(P<0.001)。(2)RA组PBMC中KMO基因表达水平与疾病活动指数28评分、血沉、类风湿因子呈正相关(r_(s)=0.417,P=0.038;r=0.545,P=0.005;r_(s)=0.433,P=0.031),与C反应蛋白、抗环瓜氨酸多肽抗体无相关性。(3)RA组滑膜组织中KMO表达高于HC组,差异有统计学意义(P<0.01);RA组滑膜组织FLS中KMO表达高于HC组,差异有统计学意义(P<0.001)。结论RA患者PBMC、滑膜组织及FLS中KMO表达增加,且KMO基因表达水平与RA患者疾病活动性相关,提示KMO可能促进RA病程。 Objective To investigate the expression and clinical significance of kynurenine-3-monooxygenase(KMO)in peripheral blood mononuclear cells(PBMC),synovial tissue,and fibroblastic-like synovial cells(FLS)of rheumatoid arthritis(RA)patients.Methods Peripheral blood samples from 25 healthy control(HC)individuals and 25 patients diagnosed with RA were collected,and real-time fluorescence quantitative PCR and Western blot were used to detect KMO gene and protein expression in PBMC of RA and HC groups,and to analyze the correlation between the expression level of the KMO gene in the PBMC of the RA patients and the indexes of the laboratory tests.Meanwhile,immunohistochemistry and immunofluorescence were used to detect KMO expression in synovial tissue and FLS in RA and HC groups.Results①KMO gene and protein expression in PBMC of RA group were higher than that of HC group,and the difference was statistically significant(P<0.001).②The level of KMO gene expression in PBMC of RA group was positively correlated with disease activity index 28 score,blood sedimentation,and rheumatoid factor(r_(s)=0.417,P=0.038;r=0.545,P=0.005;r_(s)=0.433,P=0.031),and had no correlation with C-reactive protein and anti-cyclic citrullinated polypeptide antibody.③KMO expression in synovial tissue of RA group was higher than that of HC group,and the difference was statistically significant(P<0.01);KMO expression in FLS of synovial tissue of RA group was higher than that of HC group,and the difference was statistically significant(P<0.001).Conclusion KMO expression increases in PBMC,synovial tissue and FLS of RA patients,and the level of KMO gene expression is correlated with the disease activity of RA patients,suggesting that KMO may promote the course of RA.
作者 宗雪梅 林茜茜 陈悦兰 王鑫铭 魏伟 严尚学 常艳 Zong Xuemei;Lin Qianqian;Chen Yuelan;Wang Xinming;Wei Wei;Yan Shangxue;Chang Yan(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immunological Drugs,Ministry of Education,Anhui Collaborative Innovation Center for Anti-inflammatory and Immune Drugs,Hefei 230032;Dept of Pharmacy,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Laboratory Animal Center,Anhui Medical University,Hefei 230032)
出处 《安徽医科大学学报》 北大核心 2025年第7期1218-1224,共7页 Acta Universitatis Medicinalis Anhui
基金 安徽省自然科学基金(编号:2108085MH320) 安徽省转化医学研究院科研基金项目(编号:2023zhyx-C11)。
关键词 类风湿关节炎 犬尿氨酸-3-单加氧酶 犬尿氨酸 3-羟基犬尿氨酸 外周血单个核细胞 滑膜组织 成纤维样滑膜细胞 rheumatoid arthritis kynurenine 3-monooxygenase kynurenine 3-hydroxykynurenine peripheral blood mononuclear cells synovial tissue fibroblast-like synoviocytes
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