蜕膜自然杀伤细胞在子痫前期发病机制中的研究进展

doi:10.12280/gjfckx.20240952

摘要/Abstract

摘要：

子痫前期（preeclampsia，PE）是妊娠期特有的疾病，是孕产妇和围产儿发病和死亡的主要原因。目前PE的病因和发病机制尚未完全阐明，滋养细胞侵袭不足和子宫螺旋动脉重塑障碍是导致PE发病的重要因素。有研究表明，蜕膜自然杀伤（decidual natural killer，dNK）细胞具有参与子宫螺旋动脉重塑、调控滋养细胞入侵、参与母胎界面免疫耐受、促进胎儿生长等作用。dNK细胞数量、功能和表型等的变化，dNK细胞与绒毛外滋养细胞上配体结合的相应受体表达异常，dNK细胞分泌的细胞因子的变化，可能是PE发病的原因。综述dNK细胞在PE发生发展中的作用，为PE的诊断和治疗提供可靠的理论依据。

关键词: 先兆子痫, 蜕膜, 杀伤细胞, 天然, 子宫螺旋动脉, 血管重塑, 滋养层

Abstract:

Preeclampsia (PE) is a pregnancy-specific disorder that is a leading cause of maternal and perinatal morbidity and mortality. At present, the etiology and pathogenesis of PE remain incompletely understood, although insufficient trophoblast invasion and impaired uterine spiral artery remodeling are considered major contributing factors. Studies suggest that decidual natural killer (dNK) cells play crucial roles in uterine spiral artery remodeling, regulating trophoblast invasion, mediating maternal-fetal interface immune tolerance, and promoting fetal growth. Alterations in dNK cell number, function, and phenotype, aberrant expression of receptors for ligands on extravillous trophoblasts, and changes in the cytokine profile secreted by dNK cells may contribute to the development of PE. This review summarizes the role of dNK cells in the pathogenesis of PE, providing a theoretical basis for improved diagnosis and treatment.

Key words: Pre-eclampsia, Decidua, Killer cells, natural, Spiral arterys, Vascular remodeling, Trophoblasts

王晶, 王永红. 蜕膜自然杀伤细胞在子痫前期发病机制中的研究进展[J]. 国际妇产科学杂志, 2025, 52(1): 88-93.

WANG Jing, WANG Yong-hong. Decidual Natural Killer Cells in the Pathogenesis of Preeclampsia: A Review[J]. Journal of International Obstetrics and Gynecology, 2025, 52(1): 88-93.

图/表 2

图1 子宫螺旋动脉重塑过程中VSMC的渐进转变[22] 注：A 在非妊娠期，VSMC在月经周期中保持不变，子宫内膜中存在少量NK细胞和巨噬细胞。B 子宫内膜间质细胞在胚胎植入后蜕膜化，并启动VSMC的形态转化。C dNK细胞和蜕膜巨噬细胞被募集到蜕膜，增强了VSMC的分离。D EVT侵入并与dNK细胞和蜕膜巨噬细胞协同作用，诱导VSMC去分化。重塑子宫螺旋动脉周围具有VSMC和dNK细胞双重特征的细胞（粉红色细胞）。E 子宫螺旋动脉周围VSMC消失。Unremodeled spiral artery 未重塑的子宫螺旋动脉；Non-pregnant stage 非妊娠期；Un-remodeled stage with DSC 蜕膜基质细胞出现的未重塑阶段；Un-remodeled stage with DSC and immune cells 蜕膜基质细胞和免疫细胞出现的未重塑阶段；Remodeling spiral artery 重塑过程中的子宫螺旋动脉；Remodeling stage with EVTs 绒毛外滋养细胞出现的重塑阶段；Remodeled spiral artery 重塑的子宫螺旋动脉；Fully remodeled stage 重塑完成阶段；Internmediate transition cells 中间过度细胞；decidual EVTs 蜕膜绒毛外滋养细胞；Macrophages 巨噬细胞；Decidual stromal cells 蜕膜基质细胞；Dedifferentiated cells 去分化细胞；dNKs with H3K4dime modification H3K4dime修饰的dNKs。

图2 dNK细胞在PE发病中的作用注：KIRs 杀伤细胞免疫球蛋白样受体；LILRB1 白细胞免疫球蛋白样受体B1；MMPs 基质金属蛋白酶；Ang-1 血管生成素-1；Ang-2 血管生成素-2；VEGF 血管内皮生长因子；IFN-γ γ干扰素；M-CSF 巨噬细胞集落刺激因子；IP-10 IFN诱导蛋白-10；Spiral artery remodeling 子宫螺旋动脉重塑；Trophoblast invasion 滋养细胞侵袭。

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