趋化因子CXCL1与脊柱关节病外周关节炎及病因相关性研究

Studies on the relationship of CXCL1 and peripheral arthritis in spondyloarthropathy and its pathogenesis

目的探讨趋化因子在诱导脊柱关节病(SpA)外周关节炎症中的作用。方法分别在体外应用5例SpA患者的关节滑液诱导5名健康志愿者的外周血单个核细胞(PBMC)1.5h,提取总RNA后,应用基因芯片技术中的Superarray芯片技术筛选分别含有96个目的细胞因子和趋化因子的基因表达谱。应用ELISA技术分别检测54例强直性脊柱炎(AS)患者和30例健康者(正常对照组)外周血CXCL1的蛋白表达水平;比较33例SpA和14例骨关节炎(OA)患者关节液中CXCL1的表达水平,同时还检测生物制剂英利昔单抗治疗前后CXCL1的蛋白表达水平。结果在关节液刺激后,基因芯片筛选出PBMC中的CXCL1、CXCL2、CXCL3和IL-8基因表达增高2倍以上,炎性细胞因子(如TNF-α、IL-6、IL-1等)和其他趋化因子的表达并未随关节液的刺激而增加;ELISA结果发现AS患者外周血中CXCL1的蛋白水平显著高于正常对照组(P<0.01);SpA患者关节液中的CXCL1蛋白表达水平也显著高于OA患者(P<0.01)。结论CXCL1在诱导脊柱关节病外周关节炎症和在脊柱关节病的发病机制中发挥一定的作用。

Objective To investigate the role of chemnkine in inducing peripheral arthritis in spondyloarthropathy （SPA）. Methods Microarray was used to screen the candidates of inducing peripheral arthritis in SpA, and enzyme linked immunosorbent assay（ELISA） was used to verify the results. Peripheral blood mononuclear cells （PBMC） from 5 healthy subjects were co-incubated 1.5 hours with synovial fluid of 5 patients with SpA, total RNA were then extracted, and the samples were screened for the target genes by using superarray techniques. ELISA was used to determine CXCL1 protein levels of 54 ankylosing spondylitis （AS） patients and 30 healthy controls, also to determine the CXCL1 levels of synovial fluids from 33 SpA patients and 14 osteoarthritis （OA） patients, and to determine CXCL1 protein levels by ELISA before and after treatment with infliximab. Results The expression of CXCL1, CXCL2, CXCL3 and IL-8 were more than 2 fold higher after stimulated by synovial fluids. However, there was no change in other chemokines and cytokines, such as TNFα, IL-6 and 1L-1 after stimulation. The protein level of CXCL1 was significant higher in serum of patients with AS than that of healthy control （P〈0. 01）. The concentration of CXCL1 was also significantly higher in synovial fluid from patients with SpA than that of OA （ P〈0. 01）. Conclusions CXCL1 may play an important role in inducing peripheral arthritis and participate in the pathogenesis of SpA.