健康妊娠和子痫前期血浆血栓炎症表达谱的差异分析

Analysis of thromboinflammatory response expression profile in pregnancy and preeclampsia

目的观察正常妊娠过程和子痫前期(PE)血栓炎症性反应差异,为PE的早期诊断和预防策略改进提供工作基础。方法定制抗体芯片(覆盖大量细胞因子、止血相关蛋白质等)检测健康育龄女性、健康妊娠女性和子痫前期患者血浆,分析各组间差异蛋白质特征。结果健康妊娠组和健康育龄组有37种蛋白质水平差异有统计学意义,相对于健康育龄组,健康妊娠组有解整合素-金属蛋白酶12、趋化因子CCL2等16种蛋白质水平升高,粒-单细胞集落刺激因子(GM-CSF)和载脂蛋白F等21种水平降低;PE组和健康妊娠组有27种蛋白质水平差异存在统计学意义,相对于健康妊娠组,PE组有GM-CSF和血管内皮生长因子受体2(VEGFR2)等16种水平升高,肿瘤坏死因子相关凋亡诱导配体、干扰素Ω1等11种水平降低。进一步综合分析健康育龄组、健康妊娠组和PE组血浆蛋白质发现,PE患者血浆蛋白质出现更复杂的变化,更多参与炎症和免疫反应的细胞因子和急性期反应蛋白水平升高,更多控制炎症反应的细胞因子水平降低,促进血栓形成和参与补体反应的蛋白质水平升高,肾素水平降低以及VEGFR2水平升高。结论 PE存在着比与健康妊娠更严重的炎症反应、止血和血管内皮系统失衡,提示研究PE的血栓炎症反应将有助于改进PE的诊断和预防策略。

Objective To explore the differences of thromboinflammatory response between healthy pregnancy and preeclampsia(PE) and provide potential strategies for diagnosis and prevention of PE. Methods The antibody microarray was prepared to detect plasma protein expression profile of non-pregnant women, healthy pregnant women and preeclampsia patients. The differentially expressed proteins were identified and analyzed. Results The levels of 37 proteins were significantly different between non-pregnant and healthy pregnant women, among which 16 proteins were increased, such as disintegrin, metalloproteinase domain-containing protein 12 and C-C motif chemokine 2, while 21 proteins were decreased, such as GM-CSF and apolipoprotein F. The levels of 27 proteins were significantly different between healthy pregnant women and preeclampsia patients, among which 16 proteins were increased, such as GM-CSF and VEGFR2 and 11 proteins were decreased, such as tumor necrosis factor-related apoptosis-inducing ligand and interferon Omega 1. Further analysis found that PE patients group presented more complicated changes compared with healthy pregnant women. PE group included more significantly increased proteins which involved in inflammation and immune responses and elevated levels of acute phase reaction, while the levels of more anti-inflammation cytokines decreased significantly. In the plasma of PE patients more proteins participating thrombosis and complement reaction increased significantly. Also, renin level was significantly dropped and VEGFR2 was elevated. Conclusion More serious inflammatory response, hypercoagulable status and imbalance of angiogenesis and anti-angiogenesis may exist in PE, which should be helpful for further improving potential strategies in diagnosis and prevention of PE.