类风湿关节炎炎性关节中高水平脂联素促进白细胞介素-6单核细胞趋化因子-1和核因子-κB受体活化因子配体表达  

High levels of adiponectin in the inflammatory joint of rheumatoid arthritis contribute to elevated interleukin-6, monocyte chemoattractant proteins-1 and receptor activator for nuclear factor κB ligand expression

作　　者：谈文峰[1] 徐凌霄[1] 王芳[2] 郭敦明[3] 刘婷[5] 何韶衡[4] 张缪佳[1] 

机构地区：[1]南京医科大学第一附属医院风湿免疫科,210029 [2]南京医科大学第一附属医院心血管病科,210029 [3]南京医科大学第一附属医院骨科,210029 [4]南京医科大学第一附属医院临床实验研究中心,210029 [5]南京医科大学附属无锡人民医院风湿免疫科

出　　处：《中华风湿病学杂志》2010年第9期592-596,657,共6页Chinese Journal of Rheumatology

基　　金：基金项目：国家自然科学基金青年基金（30701129,30901332）;国家中医药局青年科学基金（06-07JQ06）;江苏省自然科学基金（BK2007255）;中华医学会研究基金（08010090087）;美国关节炎基金会Meyer青年基金

摘　　要：目的 研究类风湿关节炎（RA）炎性关节中高水平脂联素（AD）表达的意义.方法 酶联免疫吸附试验（ELISA）测定关节液中AD及白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子（TNF）-α、单核细胞趋化因子（MCP）-1和基质金属蛋白酶（MMP）-9等促炎因子/趋化因子的含量,并分析AD与其相关性.双重免疫标记分析RA滑膜中AD在滑膜成纤维细胞（SFLs）、T淋巴细胞、单核细胞、中性粒细胞和肥大细胞的表达.ELISA测定重组AD因子刺激SFLs后培养上清液中细胞因子含量变化.实时荧光定量反转录-聚合酶链反应（real-time PCR）分析AD和IL-6共刺激对人滑膜细胞系MH7A中核因子-κB受体活化因子配体（RANKL）mRNA表达影响.3组间采用多变量方差分析,2组比较采用Student＇s t检验.Mann-Whitney U检验,相关性分析采用Spearman检验.结果 RA关节液中AD与IL-6含量呈正相关（r=0.27,P=0.03）.AD与成纤维细胞双重免疫标记呈阳性反应.以重组AD因子30g/ml刺激SFLs 24 h后,培养上清液中IL-6和MCP-1分泌量与刺激前相比分别增加了11.4倍和8倍（P〈0.05）.AD和IL-6共刺激后,MH7A中RANKL mRNA表达显著增加（82±26）.结论 炎性关节中高水平AD可促进IL-6、MCP-1和RANKL表达,其可能在RA慢性炎症和骨侵蚀过程中发挥重要作用.Objective To explore the potential role of high levels of adiponectin （AD） in the inflammatory joint of rheumatoid arthritis （RA）. Methods ELISA was used to measure the levels of AD, IL-Iβ,IL-6, IL-8, TNF-α, MCP-1 and MMP-9 in the synovial fluids of RA and osteroarthritis （OA）, the levels of these cytokines were tested after the synovial fibroblasts （SFLs） were stimulated with AD. Doublelabeling immunohistochemistry was used to analyze the expression of AD in RA synovium. Cytokines were measured by ELISA after SFLs were stimulated with AD. The expression of RANKL was detected by real-time PCR after MH7A were treated with AD and IL-6 ANOVA, Student＇s t-test, Mann-Whitney U-tese, Spearman＇s-test were used for statistical analysis. Results High levels of AD in RA synovial fluids were correlated with IL-6 levels. Double labeling immunohistochemistry showed that AD was localized in fibroblasts. MCP-1 and IL-6 were dramatically increased in human synovial fibroblasts following incubation with recombinant AD for 24 h. RANKL mRNA was significantly increased in MH7A after treated with AD and IL-6. Conclusion High levels of AD in the inflammatory joints of RA are likely to contribute to the high expression of IL-6, MCP-1 and RANKL, which may play an important role in the chronic inflammation, osteoclasts activation and bone erosion in RA.

关 键 词：关节炎 类风湿 白细胞介素6 单核细胞化学吸引蛋白质类 

分 类 号：R686[医药卫生—骨科学]