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幼年特发性关节炎患儿基质金属蛋白酶及细胞因子的改变及意义

Changes of matrix metalloproteinase and cytokines and its clinical significance in children with juvenile idiopathic arthritis

摘要目的 探讨幼年特发性关节炎(JIA)多关节型患儿血清及关节液基质金属蛋白酶(MMP)-I、MMP-3、金属蛋白酶抑制剂(TIMP)-1、白细胞介素(IL)-1、肿瘤坏死因子(TNF)-α,转化生长因子(TGF)-β水平的变化及临床意义.方法 酶联免疫吸附试验(ELISA)检测32例多关节型JIA患儿及28例对照组(外伤性关节炎患儿)血清及关节液中MMP-1、MMP-3、TIMP-1、IL-1、TNF-α、TGF-β的水平.同时检测血白细胞计数、C反应蛋白(CRP)、红细胞沉降率(ESR)及类风湿因子(RF)水平.统计学方法采用两个独立样本的t检验及Pearson直线相关分析.结果 ①JIA组血清MMP-1、MMP-3、IL-1、TNF-α水平分别为(158±67) ng/ml、(212±89) ng/ml、(39±19) pg/ml、(26±10) pg/ml,明显高于对照组(P均<0.05),MMP-3/TIMP-1为0.86±0.32,亦较对照组升高(P<0.05),TIMP-1、TGF-β水平分别为(248±88)、(17±9)ng/ml,明显低于对照组(P均<0.05);血清MMP-3、MMP-3/TlMP-1与白细胞计数、CRP、ESR呈正相关(P均<0.05).②JIA组关节液MMP-1、MMP-3、IL-1、TNF-α水平分别为(216±78) ng/ml、(766±291) ng/ml、(56±21) pg/ml、(36±14) pg/ml,明显高于对照组(P均<0.05),MMP-3/TIMP-1为2.68±0.89,亦较对照组明显升高(P<0.05),TIMP-1、TGF-β水平分别为(286±88)、(12±4) ng/ml,明显低于对照组(P均<0.05).③JIA组关节液MMP-1、MMP-3、TIMP-1、IL-1、TNF-α水平明显高于其血清水平(P均<0.05),TGF-β水平则明显低于其血清水平(P<0.05).结论 血清及关节液中MMP-1、MMP-3、IL-1、TNF-α水平升高,TIMP-1永平降低,参与了JIA多关节型的发病过程,TGF-β水平降低,在其发病中可能起保护作用.血清MMP-3/ⅡMP-1比值与JIA炎性指标呈正相关,有助于判断病情活动性.

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abstractsObjective The purpose of the study was to investigate the changes and clinical significance of matrix metalloproteinase (MMP)-1,MMP-3,tissue inhibitor of metalloproteinase (TIMP),interleukin (IL)-1,tumor necrosis factor (TNF)-α and transforming growth factor(TGF)-β in juvenile idiopathic arthritis (JIA).Methods Thirty-two JIA subjects and 28 controls (traumatic arthritis patients) were included into this study.The MMP-1,MMP-3,TIMP,IL-1,TNF-α and TGF-β level in the serum and synovia were assessed by ELISA.The WBC count,the level of CRP,ESR,RF were also detected.Independent t-test and Pearson's analysis were adopted for data analysis.Results ① The level of MMP-1,MMP-3,IL-1 and TNF-α in the serum was (158±67) ng/ml,(212±89) ng/ml,(39±19) pg/ml,(26±10) pg/ml respectively,which was significantly higher than that of the control group (all P<0.05) ; the ratio of MMP-3/TIMP-1 (0.86±0.32) was higher in the study group than that of the control group (P<0.05),while the value of TIMP-1,TGF-β was (248±88),(17±9) ng/ml respectively,which was lower than that of the control group (P<0.05).The value of seral MMP-3,MMP-3/TIMP-1 was positively correlated with that of WBC,CRP,ESR in the JIA group (all P<0.05).② The value of MMP-1,MMP-3,IL-1 and TNF-α in the synovia was (216±78) ng/nl,(766±291)ng/ml,(56±21) pg/ml,(36±14) pg/ml respectively,which was higher than that of the control group (all P<0.05); the ratio of MMP-3/TlMP-1 (2.68±0.89) was higher than that of the control group (P<0.05),while the value of TIMP-1,TGF-β was (286±88) ng/ml,(12±4) ng/ml respectively,which was lower than that of the control group (all P<0.05).③ The value of MMP-1,MMP-3,TIMP-1,IL-1 and TNF-α in the synovia was higher than that in the serum (all P<0.05),while the value of TGF-β was lower than that in the serum (P<0.05).Conclusion The value of MMP-1,MMP-3,IL-1 and TNF-α increases both in the serum and synovia,while the value of TIMP-1 decreases.The value of TGF-β decreases,which may have protective effect on JIA.The ratio of MMP-3/TIMP-1 in the serum is positively correlated to inflammation parameters,which may be used to judge the activity of illness in JIA.

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