Zhu Fubing, Liu Jian, Wang Guizhen, Fang Li, Zhang Pingheng, Tan Bing
Anhui University of Chinese Medicine, Hefei 230038, China.
Department of Rheumatism Immunity, First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, China. *Corresponding author, E-mail:
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Oct;32(10):1366-1371.
Objective To explore the relationship between Xinfeng Capsule (XFC) improving the hypercoagulative state in patients with Sjogren's syndrome (SS) and miR-155/suppressor of cytokine signaling 1 (SOCS1)/nuclear factor κB (NF-κB) signaling pathway. Methods Sixty-six SS patients were randomly divided into XFC-treated group and hydroxychloroquine (HCQ)-treated control group (n=33 per group), which were respectively treated with XFC and HCQ. In addition, 20 healthy volunteers were enrolled as a normal control group. The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIG), thrombin time (TT) and D-dimer (D-D) were detected using automatic coagulation analyzer. Interleukin-1β (IL-1β), IL-4, IL-10, tumor necrosis factor-α (TNF-α), P50, P65, inhibitor of NF-κB α (IκBα) were tested using ELISA. Meanwhile, the mRNA expressions of p50, p65 and IκBα were determined using quantitative real-time PCR, and the level of microRNA-155 (miR-155) was examined by one-step fluorescence quantitative PCR. The protein levels of P50, P65 and SOCS1 were detected using Western blotting. Erythrocyte sedimentation rate (ESR) was evaluated by Westergren method. Hypersensitive C-reactive protein (hs-CRP) was detected using automatic biochemical analyzer. Results Compared with the normal control group, the levels of D-D and FIB significantly increased in SS group; simultaneously, the serum levels of miR-155, IL-1β, TNF-α, P50, P65, IκBα, hs-CRP, ESR were significantly elevated in SS patients, while IL-4 and IL-10 were significantly reduced. Spearman correlation analysis showed that the coagulation parameters were remarkably correlated with cytokines, NF-κB and activity indexes. In the two treated groups, coagulation parameters and related indexes were demonstrated having some improvement, especially in the XFC group, which had a much higher efficiency, and better outcomes in reducing the levels of FIB, D-D, miR-155, TNF-α, IL-1β, P50, P65, ESR and hs-CRP, as well as increasing the expressions of SOCS1, IL-4 and IL-10. Conclusion XFC can significantly alleviate the hypercoagulative state of patients with SS, and the mechanisms may be related to the inhibition of miR-155/SOCS1/NF-κB signaling pathway.
目的 探讨新风胶囊（XFC）改善干燥综合征（SS）患者高凝状态与微小RNA-155/细胞因子信号转导抑制因子1（SOCS1）/核因子κB（NF-κB）信号通路之间的关系。方法 将66例SS患者随机分为XFC治疗组和羟氯喹（HCQ）治疗对照组（每组33例），分别给予XFC和HCQ治疗。另外，招募20名健康志愿者作为正常对照组。采用自动凝血分析仪检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIG）、凝血酶时间（TT）和D-二聚体（D-D）水平。采用酶联免疫吸附测定法检测白细胞介素-1β（IL-1β）、IL-4、IL-10、肿瘤坏死因子-α（TNF-α）、P50、P65、NF-κBα抑制因子（IκBα）。同时，采用定量实时聚合酶链反应测定p50、p65和IκBα的信使核糖核酸表达，采用一步荧光定量聚合酶链反应检测微小核糖核酸-155（miR-155）水平。采用蛋白质免疫印迹法检测P50、P65和SOCS1的蛋白水平。采用魏氏法评估红细胞沉降率（ESR）。采用自动生化分析仪检测超敏C反应蛋白（hs-CRP）。结果 与正常对照组比较，SS组D-D和FIB水平显著升高；同时，SS患者血清miR-155、IL-1β、TNF-α、P50、P65、IκBα、hs-CRP、ESR水平显著升高，而IL-4和IL-10显著降低。Spearman相关性分析显示，凝血参数与细胞因子、NF-κB及活性指标显著相关。在两个治疗组中，凝血参数及相关指标均有一定改善，尤其是XFC组，疗效更高，在降低FIB、D-D、miR-155、TNF-α、IL-1β、P50、P65、ESR和hs-CRP水平以及提高SOCS1、IL-4和IL-10表达方面效果更好。结论 XFC可显著缓解SS患者的高凝状态，其机制可能与抑制miR-155/SOCS1/NF-κB信号通路有关。
