基于细胞因子/NF-κB信号通路探讨强直性脊柱炎患者血液高凝状态形成的机制

Mechanism of blood hypercoagulable state in patients with ankylosing spondylitis based on cytokines and NF-κB signaling pathway

目的:观察强直性脊柱炎(AS)患者血小板、凝血指标、疾病活动性指标、细胞因子、核转录因子-κB(NF-κB)信号传导通路相关指标及临床症状的变化,探讨AS患者高凝状态形成的可能机制。方法:检测AS组(25例)和健康对照组(20例)血小板(PLT)、凝血常规+D-D、血沉(ESR)、hs-CRP,采用酶联免疫吸附法(ELISA)检测外周血血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-10、IL-17、核因子激活剂(Act1)、NF-κB抑制蛋白(IκBα)、NF-κB/P65、NF-κB/P50、血栓素A2(TXA2)、P-选择素(GMP140或CD62P)、血小板活化因子(PAF)的含量,并观察AS患者临床症状。结果:与健康对照组比较,AS组PLT、FBG、D-D、ESR、hs-CRP明显升高(P<0.01),其中PLT、FBG、D-D异常百分比分别为68%、80%、72%。与健康对照组比较,AS患者外周血血清中TNF-α、IL-1β、IL-17、Act1、IκBα、NF-κB/P65、NF-κB/P50、GMP140、PAF、TXA2的含量明显升高,IL-10的含量明显降低(P<0.05,P<0.01)。相关性分析显示,AS患者PLT、FBG、D-D、TXA2与TNF-α、IL-1β、IL-17、Act1、IκBα、NF-κB/P65、NF-κB/P50、GMP140、PAF、ESR、hs-CRP、VAS、BASDAI呈正相关(P<0.05,P<0.01);与IL-10呈负相关(P<0.05,P<0.01)。结论:AS患者血液处于高凝状态,以PLT、FBG、D-D异常升高为主。AS患者存在细胞因子紊乱、NF-κB信号通路过度活化,其可能是高凝状态的形成机制,且AS患者的高凝状态还与症状、体征相关。

Objective：To observe the changes in platelet,coagulation index,disease activity indexes,cytokines,nuclear factor（NF）-κB signaling pathway and clinical symptoms and explore the mechanism of the hypercoagulable state in patients with ankylosing spondylitis（AS）.Methods：Twenty-i ve AS patients and 20 healthy participants in the control group were enrolled in this study.Platelet（PLT）,coagulation index＋D-D,erythrocyte sedimentation rate（ESR） and hs-CRP were detected.Enzymelinked immunosorbent assay（ELISA） were used to detect tumor necrosis factor（TNF）-α,interleukin（IL）-1β,IL-10,IL-17,nuclear factor activation agent（Act1）,NF-κB inhibition protein（IκBα）,nuclear transcription factor（NF-κB）/P65,NF-κB/P50,thromboxane A2（TXA2）,P-selectin（GMP140 or CD62p） and platelet activating factor（PAF） in peripheral blood serum of participants in both groups.In addition,the laboratory parameters and clinical symptoms of AS patients were observed.Results：Compared with the control group,the indexes of PLT,FBG,D-D,ESR,and hs-CRP were significantly higher（P〈0.01）.The abnormal percentages of PLT,FBG and D-D in AS group were 68%,80% and 72% respectively.Compared with the control group,TNF-α,IL-1β,IL-17,Act1,IκBα,NF-κB/P65,NF-κB/P50,GMP140,PAF and TXA2 in patients with AS were also significantly higher,and IL-10 was significantly lower（P〈0.05,P〈0.01）.2Correlation analysis showed that in AS patients PLT,FBG,D-D and TXA2 were positively related to TNF-α,IL-1β,IL-17,Act1,IκBα,NF-κB/P65,NF-κB/P50,GMP140,PAF,ESR,hs-CRP,VAS and BASDAI（P〈0.05,P〈0.01）,but negatively correlated with IL-10（P〈0.05,P〈0.01）.Conclusion：Theblood of AS patients is in hypercoagulable state,in which the abnormal percentage of PLT,FBG and D-D were significantly higher.The formation of the hypercoagulable state in AS patients may be related to the disorder of cytokines and the excessive activation of NF-κB signaling pathway.The hypercoagulable state is also related to symptoms and signs.