文章摘要
吕连峥 蔺昕 钱雷 徐卫平 张国英.子痫前期患者外周血单核细胞Toll样受体4检测及其意义[J].,2015,15(35):6952-6955
子痫前期患者外周血单核细胞Toll样受体4检测及其意义
Expression of Toll-like Receptor 4 on Peripheral Blood Monocytes and ItsFunctional Implication in Pre-eclampsia
  
DOI:
中文关键词: 子痫前期  单核细胞  Toll样受体4
英文关键词: Pre-eclampsia  Monocyte  Toll-like receptor4
基金项目:国家自然科学基金项目(81471199)
作者单位
吕连峥 蔺昕 钱雷 徐卫平 张国英 南京中医药大学附属南京市中西医结合医院检验科南京医科大学附属南京医院(南京市第一医院)检验科滨海县人民医院检验科 
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中文摘要:
      目的:通过检测子痫前期(PE)患者外周血Toll样受体4(TLR4)表达及其分泌促炎细胞因子的功能,探讨单核细胞TLR4 在 PE 发病过程中的作用。方法:选取22 例子痫前期患者(PE 组)和23 例正常孕妇(HP 组)作为研究对象。经知情同意后抽取4 mL 静脉血,肝素钠抗凝。流式细胞术(FCM)检测单核细胞TLR4表达;脂多糖(LPS)刺激单核细胞18 小时,Luminex 液相芯片检测培 养上清液中肿瘤坏死因子(TNF)-alpha、白细胞介素(IL)-6、IL-12P70 和IL-10 浓度;并分析PE 患者单核细胞TLR4 阳性频率与外周 血清细胞因子浓度的相关性。结果:与HP 组相比,PE 组单核细胞TLR4 阳性细胞频率(TLR4+:23.2 (18.4-44.3) % vs59.7 (19.8-79.7) %)和平均荧光强度(MFI:32.3(27.6-49.2)vs48.6 (32.4- 93.2)明显升高,差异均有统计学意义(P<0.05);单核细胞经50 ng/mL LPS 刺激培养18 小时,PE 组上清液TNF-alpha(243.5± 15.2 pg/mLvs123± 81.3 pg/mL)、IL-6(3122.7 ± 534.2 pg/mLvs1380.4± 332 pg/mL)浓度明显高于HP 组,IL-10(84.2 ± 24.9 pg/mL vs164.5 ± 47.1 pg/mL)低于HP 组,差异均有统计学意义(P<0.05);PE 患 者单核细胞阳性频率与外周血清中细胞因子TNF-alpha、IL-6 具有相关性(r=0.634、r=0.528,P<0.05)。结论:PE 患者外周血单核细胞 TLR4表达明显增加,并处于活化状态,分泌较多的促炎细胞因子IL-6 和TNF-alpha,参与子痫前期的疾病过程。因此,抑制单核细胞 TLR4表达可能是治疗子痫前期的新途经。
英文摘要:
      Objective:To investigate the role of Toll-like receptor (TLR)4 on peripheral blood monocyte in the pathogenesis of pre-eclampsia (PE), the expression of TLR4 and cytokine production in peripheral blood monocytes from patients with preeclampsia were compared with those of health pregnant women.Methods:22 patients with established preeclampsia patients and 23 cases of healthy pregnant women (HP) were selected in this study. 4 mL fresh venous blood was collected into a tube containing heparin after all participants gave informed written consent. The expression levels of TLR4 on monocyte were evaluated by flow cytometry (FCM). Monocytes were stimulated with LPS for 18 hours and the concentrations of IL-6, IL-12P70, IL-10 and TNF琢in supernatants were analyzed with the method of Luminex platform. The correlation between the frequencies of TLR4+ monocytes and serum cytokine levels were also evaluated.Results:Compared to HP controls, the percentage of TLR4+ monocyte was markedly higher in PE patients(59.7 (19.8-79.7) %, vs 23.2 (18.4-44.3) %. Moreover, significantly creased mean fluorescence intensity of TLR4 was detected on monocytes from PE patients (32.3(27.6-49.2) vs 48.6 (32.4-93.2, P<0.05). Upon stimulation by LPS (50 ng/mL) for 18 hours, monocytes from PE patients produced more IL-6 (3122.7± 534.2 pg/mL vs 1380.4± 332 pg/mL), TNF-alpha(243.5± 15.2 pg/mLvs123± 81.3 pg/mL) and less IL-10 (84.2 ± 24.9 pg/mL vs164.5± 47.1 pg/mL) than the monocytes from health subjects (P<0.05). In addition, a positive correlation was found between the percentage of TLR4+ monocytes and the serum levels of IL-6 and TNF-alpha in PE patients (r=0.634, r=0.528, P<0. 05).Conclusion:Our results showed that monocytes from patients with pre-eclampsia exhibit increased TLR4 expression and produce more pro-inflammation cytokines upon LPS stimulation, which might indicate a crucial role of activated monocytes in the pathogenesis of preeclampsia. Thus, the blockade of surface TLR4 on monocytes may provide a new strategy for the treatment of preeclampsia.
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