芳香烃受体(AhR)及Th17相关细胞因子在类风湿关节炎中的表达水平及其对疾病的预测价值

Expression of Th17-associated cytokines interleukin-17 and interleukin-23 in rheumatoid arthritis and its diagnostic value for diseases

目的观察芳香烃受体(AhR)及Th17相关细胞因子在类风湿关节炎中的表达水平及其对疾病的预测价值。方法选择2014年1月—2015年12月于我院就诊的RA患者60例作为观察组,选取同期于我院进行健康体检的正常人60例作为对照组,采用酶联免疫吸附法检测血清中IL-17、IL-23及AhR的表达水平,并分析其与疾病活动度的关系。结果 RA患者血清IL-17、IL-23及AhR水平高于对照组(P<0.05)。而根据病情严重程度,RA非早期组IL-17、IL-23及AhR水平较早期组增高(P<0.05)。血清IL-17水平与除CRP以外的病情活动度指标均呈正相关关系(P<0.05)。IL-23水平与SJC、TJC、HAQ、DAS28评分呈正相关关系(P<0.05),但其他指标无明显相关性(P>0.05)。RA患者PBMC中AhR的表达水平与各项临床指标无相关性(P>0.05)。IL-17和IL-23水平与Sharp评分呈正相关关系(r=0.895,P<0.01;r=0.708,P<0.01)。AhR的表达与血清IL-17和IL-23水平呈正相关(r=0.415,P<0.01)。经荧光定量PCR检测结果显示,RA患者AhR及其下游因子CYP1A1、IL-17、FOXP3 mRNA的表达水平高于对照组(P<0.05)。且RA非早期组AhR及其下游因子CYP1A1、IL-17、FOXP3 mRNA的表达水平较早期组增高(P<0.05)。经相关关系检测,RA患者AhR及其下游因子CYP1A1、IL-17、FOXP3 mRNA的表达水平与Sharp评分呈正相关关系(r=0.715,P<0.01;r=0.734,P<0.01;r=0.812,P<0.01;r=0.755,P<0.01)。结论 Th17相关细胞因子IL-17和IL-23在RA病理生理过程中发挥重要作用,其表达增高,提示关节炎症处于活跃状态,骨质破坏较重,可作为评估RA病情的重要指标。RA患者体内AhR蛋白及其相关下游信号通路均呈高表达状态,AhR通路在RA患者的发病过程中可能发挥关键作用。

Objective To observe the expression level of aroma receptor（AhR） and Th17 related cytokines in rheumatoid arthritis and its predictive value to disease. Methods Sixty patients with RA who were treated in our hospital from January 2014 to December 2015 were selected as the observation group. Sixty healthy subjects were randomly selected as the control group. IL-17,IL-23 and AhR levels in serum were detected by enzyme-linked immunosorbent and the relationship between IL-17,IL-23 and disease activity were analyzed. Results IL-17,IL-23 and AhR levels in serum of RA patients were significantly higher than those in controls（P〈0. 05）. However,the levels of IL-17,IL-23 and AhR levels were significantly higher in the non-early RA group than in the early group（P〈0. 05）,depending on the severity of the disease. There was a positive correlation between serum IL-17 level and disease activity index except CRP（P〈0. 05）. IL-23 level was positively correlated with SJC,TJC,HAQ and DAS28 scores（P〈0. 05）,but no significant correlation was found between other indexes（P〈0. 05）. The expression level of AhR in PBMC of RA patients was not correlated with clinical indexes（P〈0. 05）. IL-17 and IL-23 levels were positively correlated with Sharp score（r = 0. 895,P〈0. 01; r = 0. 708,P〈0. 01）.The expression of AhR was positively correlated with serum IL-17 and IL-23 levels（r = 0. 415,P〈0. 01）. The expression of AhR and its downstream factors CYP1A1,IL-17 and FOXP3 mRNA in RA patients were significantly higher than those in the control group（P〈0. 05） by fluorescence quantitative PCR. The expression of AhR and its downstream factors CYP1A1,IL-17 and FOXP3 mRNA in RA group were significantly higher than those in early group（P〈0. 05）. The expression level of AhR and its downstream factors CYP1A1,IL-17 and FOXP3 mRNA in RA patients were positively correlated with Sharp scores（r = 0. 715,P〈0. 01; r = 0. 734,P〈0. 01; r = 0. 812,P〈0. 01; r = 0. 755,P〈0. 01）. Conclusion The Th17-related cytokines IL-17 and IL-23 play an important role in the pathophysiology of RA,and the expression of Th17-associated cytokines is increased,suggesting that arthritis is active and bone destruction is serious. The AhR protein and its associated downstream signaling pathways are highly expressed in RA patients,and the AhR pathway may play a key role in the pathogenesis of RA patients.