子痫前期患者外周血中间型单核细胞的变化及其意义
Changes of intermediate monocytes in peripheral blood of patients with preeclampsia and their significance
目的:探讨中间型单核细胞在子痫前期发病过程中的作用。方法选择2014年10月至2015年10月在江苏省盐城市滨海县人民医院诊断为子痫前期的孕妇52例,同期健康孕妇42例和健康未孕女性42例作为对照组。采用流式细胞技术检测外周血中间型单核细胞比例,及其细胞表面Toll样受体(Toll-like receptor,TLR)2、TLR4、CD64和髓系细胞触发受体-1(triggering receptor expressed on myeloid cell-1,TREM-1)的表达(以阳性细胞比例和平均荧光强度表示),以及中间型单核细胞内肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素(interleukin,IL)-6含量(以平均荧光强度表示)。液相芯片技术检测各组血清IL-6、IL-1β、TNF-α、IL-8和IL-12P70浓度。采用两独立样本t检验、单因素方差分析、Mann-Whitney U检验、Kruskal-Wallis检验和Pearson相关分析进行统计学处理。结果子痫前期组中间型单核细胞比例为10.4%(5.3%~19.9%),高于健康孕妇组[6.6%(4.9%~7.8%)],2组均高于健康未孕组[3.8%(2.4%~5.0%)](P值均<0.01)。子痫前期组TLR4[(60.1±12.5)%与(24.9±8.8)%]和CD64阳性中间型单核细胞比例[(85.3±5.4)%与(67.4±7.5)%]均高于健康孕妇组,中间型单核细胞表面TLR4(50.3±10.2与26.8±8.6)、TREM-1(35.6±4.1与28.6±4.7)和CD64的平均荧光强度(39.8±5.2与28.9±4.8)也高于健康孕妇组(t值分别为15.416、13.437、11.898、7.707和10.454,P值均<0.01)。子痫前期组中间型单核细胞内IL-6和TNF-α的平均荧光强度分别为32.3±4.7和44.6±6.3,均高于健康孕妇组(分别为28.6±3.5和36.7±8.3)(t值分别为4.239和5.245,P值均<0.01)。子痫前期组血清IL-6、IL-8和TNF-α浓度高于健康孕妇组和健康未孕组,差异均有统计学意义(P值均<0.05)。子痫前期组中间型单核细胞比例与血清IL-6和TNF-α浓度呈正相关(r值分别为0.397和0.347,P值均<0.05)。结论子痫前期患者外周血单核细胞向中间型极化,并处于活化状态,高表达TLR4、TREM-1和CD64,分泌较多的促炎细胞因子IL-6和TNF-α,可能参与子痫前期的疾病过程。
更多ObjectiveTo explore the role of peripheral blood intermediate monocytes in the pathogenesis of preeclampsia.MethodsFifty-two patients with established preeclampsia in Binhai County People's Hospital from October 2014 to October 2015, 42 healthy pregnant women and 42 healthy non-pregnant women were enrolled in this study. The percentage of intermediate monocyte subsets, ratio of positive cells and mean fluorescence intensity (MFI) of Toll-like receptor (TLR) 2, TLR4, CD64, and triggering receptor expressed on myeloid cell-1(TREM-1), and MFI of intracellular tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were evaluated by flow cytometry. The concentrations of IL-6, IL-8, IL-1β, IL-12P70 and TNF-α in serum were analyzed using Luminex liquid phase chip technology. Independent two samplest-test, analysis of variance, Mann-WhitneyU test, Kruskal-Wallis test and Pearson correlation analysis were used for statistical analysis.ResultsPercentage of intermediate monocytes was higher in preeclampsia patients [10.4%(5.3%-19.9%)]than in healthy pregnant women [6.6%(4.9%-7.8%)], and both were higher than in non-pregnant women [3.8%(2.4%-5.0)%](allP<0.05). The ratio of TLR4 and CD64 positive intermediate monocytes [(60.1±12.5)%vs (24.9±8.8)%; (85.3±5.4)% vs (67.4±7.5)%](t were 15.416 and 13.437, bothP<0.05), and MFI of TLR4 (50.3±10.2 vs 26.8±8.6), TREM-1(35.6±4.1 vs 28.6±4.7) and CD64 (39.8±5.2 vs 28.9±4.8) (t were 11.898, 7.707 and 10.454, allP<0.05) were higher in preeclampsia patients than in healthy pregnant women. MFI of intracellular IL-6 (32.3±4.7 vs 28.6±3.5) and TNF-α (44.6±6.3 vs 36.7±8.3) in intermediate monocytes of preeclampsia patients was also significantly higher than that of healthy pregnant women (t were 4.239 and 5.245, bothP<0.05). Serum concentrations of IL-6, IL-8 and TNF-α were higher in preeclamptic patients than in healthy pregnant women and non-pregnant women (allP<0.05). Furthermore, a positive correlation was found between the percentage of intermediate monocytes and the serum levels of IL-6 and TNF-α in preeclamptic patients (r were 0.397 and 0.347, bothP<0.05).ConclusionsMonocyte subpopulations from preeclamptic patients are abnormally skewed toward intermediate monocytes which have high expressions of TLR4, TREM-1 and CD64, and secret more proinflammatory cytokines such as IL-6 and TNF-α. Therefore, intermediate monocytes are specifically altered in preeclamptic patients and may play a role in the pathophysiology of preeclampsia.
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