基于细胞因子/ NF鄄资B 信号通路探讨干燥综合征患者高凝状态的机制

目的:观察干燥综合征(SS)患者凝血参数及外周血细胞因子、NF-B 信号通路蛋白、实验室指标的变化,探讨SS 患者高凝状态的机制。方法:随机选取60 例SS 患者及20 例健康人分别作为研究组和对照组;采用全自动凝血仪测定两组凝血参数指标[活化部分凝血酶时间(APTT) 、血浆凝血酶时间(PT)、血浆纤维蛋白原(FIB)、凝血酶原时间(TT)、D-二聚体(D-D)];酶联免疫吸附法(ELISA) 检测外周血血清中细胞因子(IL-1 、TNF 、IL-10)及NF-B 信号通路蛋白(p65、p50、I B )的表达量;魏氏法测定血沉(ESR);采用全自动生化分析仪测定免疫蛋白(IgG、IgA、IgM、GLO)、超敏C 反应蛋白(hs-CRP)。结果:60 例SS 患者中凝血参数指标至少有一项异常者为46 例,占全部患者的76.7%。其中参数异常率最高的为D-D,其次依次为FIB、APTT、PT、TT。与正常组比较,SS 组凝血指标FIB、D-D,血清IL-1 、TNF 、P50、P65 表达量和实验室指标Hs-CRP、ESR、IGg、GLO、ESSDAI、角膜荧光染色积分显著升高,唾液流率、泪膜破裂时间、血清IL-10 表达量明显降低(P<0.05或P<0.01)。相关性分析显示,凝血指标FIB 与唾液流率、TNF 、P50、P65、ESR、hs-CRP 呈正相关,与IL-10 呈负相关;TT 与TNF 呈负相关;D-D 与TNF 、IL-1 、P65、ESR、hs-CRP、ESSDAI、角膜染色评分呈正相关,与IL-10 呈负相关。结论:SS 患者普遍存在高凝状态,可能与细胞因子失衡,NF-B 信号通路异常活化,从而介导血管内皮细胞损伤,引起凝血/ 纤溶系统紊乱有关。

Mechanism study of hypercoagulative state based on cytokines-NF-kappa B signaling pathway in Sjogren’s syndrome patients

Objective:To observe the changes in coagulation parameters,peripheral blood cytokines,NF-kappa B signaling pathway protein, laboratory indexes in Sjogren’s syndrome ( SS) patients, thus to explore the mechanism of hypercoagulable State.Methods: 60 patients with SS and 20 healthy persons were randomly selected as the study group and the control group;Automatic coagulation analyzer was used to detect the value of coagulation parameters [activated partial thromboplastin time (APTT),prothrombin time (PT),plasma fibrinogen ( FIB),prothrombin time ( TT),D-dimer ( DD)]; ELISA method was performed to observe the expression of related cytokines(IL-1 ,TNF ,IL-10) and NF-B signaling pathway proteins (p65,p50,I-B ); Westergren method was used to determine erythrocyte sedimentation rate (ESR),and automatic biochemical analyzer to examine immune protein(IgG,IgA, IgM,GLO) and high sensitivity C-reactive protein (hs-CRP).Results: Blood coagulation parameters in 60 patients with SS were at least one abnormal for 46 cases,accounting for 76.7% of the subjects.Among them,the abnormal rate of D-D was the highest,followed by FIB,APTT,PT,TT.Compared with the control group,D-D,FIB were significantly increased in SS patients,and TT,PT,APTT was not found obviously different.In addition,IL-1,TNF ,P50,P65,I B and inflammatory indexes like ESR,hs-CRP,IGg,GLO,ESSDAI,corneal staining score increased while the salivary flow rate,tear film break up time and IL-10 decreased significantly(P<0.05 or P<0.01).Correlation analysis showed that the coagulation parameters FIB were positively correlated with the salivary flow rate,TNF ,P50,P65,ESR,hs-CRP,while negatively correlated with IL-10,that TT was negatively correlated with TNF ;that D-D was positively correlated with TNF , IL-1 , P65, ESR, hs-CRP, ESSDAI and corneal staining score, while negatively correlated with IL-10.Conclusion: SS patients generally have hypercoagulable state,and may be associated with the imbalance of cytokines,abnormal activation NF-kappa B signaling pathway,which mediates vascular endothelial cell damage,causing coagulation/ fibrinolytic system disorders.