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  

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

作　　者：孙丽娜[1,2] 杜晓晓 张红娟 孟金来 SUN Lina;DU Xiaoxiao;ZHANG Hongjuan;MENG Jinlai(Shandong University of Traditional Chinese Medicine,Jinan 250013,Shandong,China;Department of Obstetrics and Gynecology,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250021,Shandong,China;Department of Obstetrics and Gynecology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,Shandong,China;Department of Obstetrics and Gynecology,Tengzhou Maternal and Child Health Hospital,Tengzhou 277599,Shandong,China)

机构地区：[1]山东中医药大学,山东济南250014 [2]山东大学附属省立医院妇产科,山东济南250021 [3]山东第一医科大学附属省立医院妇产科,山东济南250021 [4]滕州市妇幼保健院妇产科,山东滕州277599

出　　处：《山东大学学报（医学版）》2022年第6期41-45,共5页Journal of Shandong University:Health Sciences

基　　金：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)

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。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.

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 

分 类 号：R714.244[医药卫生—妇产科学]