TLR4/MyD88非依赖信号通路在强直性脊柱炎患者中的表达及临床意义

Expression and clinical significance of TLR4/MyD88 independent signaling pathway in patients with ankylosing spondylitis

目的检测细胞Toll样受体4(TLR4)/髓样分化因子88(MyD88)非依赖信号通路在强直性脊柱炎(AS)患者血清及滑膜组织的表达情况,探讨TLR4/MyD88非依赖信号通路在AS起病及病情活动中的作用,为治疗AS提供新思路。方法选取2019年1月至2021年12月在蚌埠医学院第二附属医院风湿免疫科就诊的AS患者46例作为AS组,选取同期健康体检者30例作为健康对照组;选取13例行髋关节置换术AS患者滑膜组织作为AS手术组,选取10例同期髋关节创伤性骨折患者滑膜组织作为对照组。检测2组研究对象血清γ-干扰素(IFN-γ)水平,分析IFN-γ与C反应蛋白(CRP)、红细胞沉降率和AS病情活动度评分(ASDAS)-CRP的相关性;采用实时荧光定量聚合酶链反应法测定2组患者滑膜组织TLR4/MyD88非依赖信号通路相关分子——TLR4、Toll样受体相关分子、TIR域含适配器诱导β-干扰素、核因子-κB-p65及末端炎症因子——IFN-γmRNA表达情况。结果AS组患者血清IFN-γ水平明显高于健康对照组,血清IFN-γ水平与红细胞沉降率、CRP、ASDAS-CRP水平均呈正相关,AS手术组患者滑膜组织TLR4/MyD88非依赖信号通路重要节点分子——TLR4、Toll样受体相关分子、TIR域含适配器诱导β-干扰素、核因子-κB-p65、IFN-γmRNA表达水平均明显高于对照组,差异均有统计学意义(P<0.05)。结论TLR4/MyD88非依赖信号通路可能在AS起病及病情活动中起到重要作用,为治疗AS提供了新思路。

Objective To investigate the expression of TLR4/MyD88 independent signal pathway in serum and synovial tissue of the patients with ankylosing spondylitis(AS),and to explore the role of TLR4/MyD88 independent signal pathway in the onset and activity of AS to provide the new ideas for the treatment of AS.Methods Forty-six patients with AS treated in the Second Affiliated Hospital of Bengbu Medical College from Janaury 2019 to December 2021 were selected as the AS group,and the healthy subjects undergoing physical exmination at the same tine were selected as the healthy control group.The synovial tissue in 13 AS cases of hip replacement was selected as the AS operation group and the synovial tissue of 10 patients with hip joint traumatic fracture was selected as the control group.The serum IFN-γlevel in the two groups was detected,and the correlation between IFN-γwith CRP,ESR and ASDAS-CRP was analyzed.The mRNA expression levels of TLR4/MyD88 non-dependent signaling pathway related molecules TLR4,TRAM,TRIF,NF-κB-p65 and IFN-γin the patients with AS were determined by real-time fluorescence quantitative PCR.Results(1)The serum IFN-γlevel in the patients with AS was significantly higher than that in the healthy control group.The serum IFN-γlevel in AS patients was positively correlated with ESR,CRP and ASDAS-CRP(P<0.001).The mRNA expression levels of TLR4,TRAM,TRIF,NF-κB-p65 and IFN-γin synovium tissues of the AS group were significantly higher than those in the control group,and the differences were statistically significant(P<0.001).Conclusion TLR4/MyD88 independent signaling pathway may play an important role in the onset and activity of AS,which may provide the new ideas for the treatment of AS.