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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (6): 41-45.doi: 10.6040/j.issn.1671-7554.0.2021.1333

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人类白细胞抗原G调控蜕膜自然杀伤细胞促进滋养细胞侵袭

孙丽娜1,2,杜晓晓3,张红娟4,孟金来2,3   

  • 发布日期:2022-06-17
  • 通讯作者: 孟金来. E-mail:sdslmjl@163.com
  • 基金资助:
    国家卫生健康委员会生育调控技术重点实验室开放课题资助项目(2021002);济南市科技发展计划项目(201805025)

Human leukocyte antigen-G promotes trophoblast invasion by regulating decidual natural killer cells

SUN Lina1,2, DU Xiaoxiao3, ZHANG Hongjuan4, MENG Jinlai2,3   

  1. 1. Shandong University of Traditional Chinese Medicine, Jinan 250013, Shandong, China;
    2. Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    3. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;
    4. Department of Obstetrics and Gynecology, Tengzhou Maternal and Child Health Hospital, Tengzhou 277599, Shandong, China
  • Published:2022-06-17

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摘要： 目的 探讨蜕膜自然杀伤(dNK)细胞对滋养细胞侵袭能力的影响,以及人类白细胞抗原G(HLA-G)调控dNK细胞影响滋养细胞侵袭的机制。 方法 收集人工流产早孕蜕膜组织11例,采用流式分选法提取dNK细胞,与HTR-8/Svneo细胞共培养,将共培养体系分为HLA-G组(n=11)和anti-HLA-G组(n=11),anti-HLA-G组加入HLA-G抗体干预。另外单独培养未作处理的HTR-8/Svneo细胞作为空白组。Transwell法检测各组HTR-8/Svneo细胞侵袭能力。ELISA法检测细胞共培养上清血管生成素-2(Ang-2)及粒细胞-巨噬细胞集落刺激因子(GM-CSF)浓度。 结果 与空白组比较,HLA-G组HTR-8/Svneo细胞侵袭能力显著降低(P<0.001)。与HLA-G组比较,anti-HLA-G组HTR-8/Svneo细胞侵袭能力显著降低(P<0.01)。细胞共培养上清细胞因子浓度检测结果显示,anti-HLA-G组细胞培养上清中Ang-2(t=2.370,P=0.028)及GM-CSF(t=2.209,P=0.039)表达水平均显著低于HLA-G组。 结论 dNK细胞可明显抑制HTR-8/Svneo细胞侵袭,HLA-G可能通过上调dNK细胞Ang-2和GM-CSF的表达促进滋养细胞侵袭。

关键词: 滋养细胞侵袭, 人类白细胞抗原G, 蜕膜NK细胞, 子痫前期, 血管生成素-2, 粒细胞-巨噬细胞集落刺激因子, 母-胎界面

Abstract: Objective To investigate the effects of decidual natural killer(dNK)cells on the invasion ability of trophoblast cells, and to explore the mechanism of human leukocyte antigen-G(HLA-G)regulating the invasion of trophoblast cells by dNK cells. Methods The first trimester decidua tissue(n=11)was obtained from women undergoing elective termination of normal pregnancies. dNK cells were extracted with flow cytometry, and co-cultured with HTR-8/Svneo cells. The co-cultured cells were divided into HLA-G group and anti-HLA-G group, which was treated with HLA-G antibodies. Additionally, untreated HTR-8/Svneo cells were cultured as the blank control. The invasion ability of HTR-8/Svneo cells was detected with Transwell assay. The concentrations of angiopoietin-2(Ang-2)and granulocyte-macrophage colony-stimulating factor(GM-CSF)in the supernatant of co-cultured cells were determined with ELISA. Results Compared with the blank control, HLA-G group had significantly reduced invasion of HTR-8/Svneo cells(P<0.001). Compared with the HLA-G group, anti-HLA-G group had significantly reduced invasion of HTR-8/Svneo cells (P<0.01). ELISA assay results of the supernatant of co-cultured cells showed that the expressions of Ang-2(t=2.370, P=0.028)and GM-CSF(t=2.209, P=0.039)were significantly lower in the anti-HLA-G group than in the HLA-G group. Conclusion dNK cells can significantly inhibit the invasion of HTR-8/Svneo cells, and HLA-G might promote the invasion of trophoblast cells by up-regulating the expressions of Ang-2 and GM-CSF in dNK cells.

Key words: Trophoblast invasion, Human leucocyte antigen-G, Decidual natural killer cell, Preeclampsia, Angiopoietin-2, Granulocyte-macrophage colony-stimulating factor, Mother-fetal interface

中图分类号: 

  • R714.2
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