子痫前期患者胎盘组织GPR124表达与螺旋动脉重铸的关系及临床研究

doi:10.3760/cma.j.cn441417-20240912-16003

摘要/Abstract

摘要：

目的　探究子痫前期（PE）患者胎盘组织中G蛋白偶联受体124（GPR124）表达与螺旋动脉重铸水平的关系及其临床意义。方法　选取2021年1月至2023年12月西安市第三医院收治的96例PE患者（PE组），年龄（33.12±5.07）岁，体重指数（27.86±2.34）kg/m²，分娩孕周（37.85±1.18）周，孕次（2.31±0.52）次，产次（1.52±0.34）次。选取同期50例健康足月孕妇作为对照，年龄（32.28±2.87）岁，体重指数（28.02±2.45）kg/m²，分娩孕周（38.13±1.12）周，孕次（2.28±0.60）次，产次（1.46±0.29）次。PE患者根据PE程度，分为轻度PE组与重度PE组。取所有受试者胎盘组织检测GPR124 mRNA和蛋白表达、胎盘螺旋动脉管壁厚度、管腔面积及血管生成因子［血管生成素2（Ang2）、血管内皮生长因子（VEGF）、胎盘生长因子（PLGF）］、炎症细胞因子［白细胞介素（IL）-6、IL-10、IL-1β、肿瘤坏死因子-α（TNF-α）］水平。Spearman或Pearson分析GPR124表达与PE患者胎盘螺旋动脉重铸、血管生成因子、炎症因子及临床特征之间的相关性。组间差异比较行t检验、LSD检验、方差分析。结果　重度PE组胎盘组织中GPR124 mRNA及蛋白表达分别为0.42±0.07、0.26±0.03，轻度PE组分别为0.51±0.11、0.34±0.05，对照组分别为1.02±0.03、0.47±0.06，3组比较差异均有统计学意义（均P<0.05）。轻度、重度PE组胎盘螺旋管壁厚度增厚，管腔面积减小，Ang2、VEGF、PLGF的mRNA表达水平低于对照组（均P<0.05）。轻度、重度PE组胎盘组织中IL-6、IL-1β、TNF-α水平高于对照组，IL-10水平低于对照组（均P<0.05）。随着PE病情程度加重，GPR124表达、胎盘螺旋管壁厚度、管腔面积及血管生成因子、炎症细胞因子水平逐渐降低或升高（均P<0.05）。PE胎盘组织中GPR124表达与胎盘螺旋动脉管壁厚度及IL-6、IL-1β、TNF-α水平呈负相关（r=-0.631、-0.562、-0.529、-0.537，均P<0.05）；与螺旋动脉管腔面积及Ang2、VEGF、PLGF、IL-10水平均呈正相关（r=0.705、0.629、0.604、0.597、0.548，均P<0.05）。GPR124表达与病情严重程度、24 h尿蛋白及入院时舒张压、收缩压均呈负相关（r=-0.605、-0.527、-0.554、-0.512，均P<0.05）。结论　胎盘组织中GPR124低表达与PE病情程度、胎盘螺旋动脉重铸、胎盘血管生成及炎症反应密切相关，可为PE诊断及病情评估提供一定指导。

关键词:

胎盘, 子痫前期, G蛋白偶联受体124, 螺旋动脉重铸, 血管生成, 炎性细胞因子

Abstract:

Objective　To investigate the relationship between the expression of G protein-coupled receptor 124 (GPR124) in placental tissue and the level of spiral artery recast in patients with preeclampsia (PE) and its clinical significance. Methods　A total of 96 patients with PE treated at Xi'an Third Hospital from January 2021 to December 2023 were selected as a PE group; they were (33.12±5.07) years old; their body mass index was (27.86±2.34) kg/m²; their gestational week at delivery was (37.85±1.18) weeks; their gestational times was 2.31±0.52; their delivery times was 1.52±0.34. Another 50 healthy full-term pregnant women during the same period were selected as the controls; they were (32.28±2.87) years old; their body mass index was (28.02±2.45) kg/m²; their gestational week at delivery was (38.13±1.12) weeks; their gestational times was 2.28±0.60; their delivery times was 1.46±0.29. The patients were divided into a mild PE group and a severe PE group according to the PE severity. The placental tissues were collected from all the subjects to detect GPR124 mRNA and protein expressions, placental spiral artery wall thickness, lumen area, and levels of angiogenic factors [angiopoietin-2 (Ang2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF)] and inflammatory cytokines [interleukin (IL) -6, IL-10, IL-1β, and tumor necrosis factor-α (TNF-α)]. Spearman or Pearson were used to analyzed the correlation of GPR124 expression with placental spiral artery recast, angiogenesis factors, inflammatory factors, and clinical features in the patients with PE. The differences between the groups were compared by t test, LSD test and analysis of variance. Results　The relative expression and protein level of GPR124 in the placental tissue in the severe PE group were 0.42±0.07 and 0.26±0.03, those in the mild PE group 0.51±0.11 and 0.34±0.05, and those in the control group 1.02±0.03 and 0.47±0.06, with statistical differences between the 3 groups (both P<0.05). The placental spiral tube wall thicknesses in the mild PE group and the severe PE group were thicker than that in control group, and the lumen area and mRNA expression levels of Ang2, VEGF, and PLGF were lower (all P<0.05). The levels of IL-6, IL-1β, and TNF-α in the mild PE group and the severe PE group were higher than those in the control group, while the level of IL-10 was lower (all P<0.05). With the aggravation of PE, the expression of GPR124, the thickness of placental spiral tube wall, the lumen area, and the levels of angiogenic factors and inflammatory cytokines gradually decreased or increased (all P<0.05). The expression of GPR124 in PE placenta tissue was negatively correlated with the thickness of placental spiral artery wall and the levels of IL-6, IL-1β, and TNF-α (r=-0.631, -0.562, -0.529, and -0.537; all P<0.05), and was positively correlated with the lumen area of spiral artery and the levels of Ang2, VEGF, PLGF, and IL-10 (r=0.705, 0.629, 0.604, 0.597, and 0.548; all P<0.05). The expression of GPR124 was negatively correlated with the severity of disease, 24 h urine protein, and diastolic and systolic blood pressures at admission (r=-0.605, -0.527, -0.554, and -0.512; all P<0.05). Conclusion　The low expression of GPR124 in placental tissue is closely related to the severity of PE, placental spiral artery recast, placental angiogenesis, and inflammatory response, which can provide certain guidance for the diagnosis and disease evaluation of PE.

Key words:

Placenta, Preeclampsia, G protein-coupled receptor 124, Spiral artery recast, Angiogenesis, Inflammatory cytokines

姚婷婷范小斌曹阳阳.

子痫前期患者胎盘组织GPR124表达与螺旋动脉重铸的关系及临床研究 [J]. 国际医药卫生导报, 2025, 31(16): 2652-2657.

Yao Tingting, Fan Xiaobin, Cao Yangyang.

Relationship between GPR124 expression in placental tissue and spiral artery recast in preeclampsia patients and clinical study [J]. International Medicine and Health Guidance News, 2025, 31(16): 2652-2657.

参考文献

[1] Roberts JM. Preeclampsia epidemiology(ies) and pathophysiology(ies)[J]. Best Pract Res Clin Obstet Gynaecol, 2024, 94: 102480. DOI: 10.1016/j.bpobgyn.2024.102480.
[2] Poon LC, Shennan A, Hyett JA, et al. The international Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention[J]. Int J Gynaecol Obstet, 2019, 145(S1): 1-33. DOI: 10.1002/ijgo.12802.
[3] Jung E, Romero R, Yeo L, et al. The etiology of preeclampsia[J]. Am J Obstet Gynecol, 2022, 226(2S): S844-S866. DOI: 10.1016/j.ajog.2021.11.1356.
[4] Chen DB, Magness RR. Vascular smooth muscle cells during spiral artery remodeling in early human pregnancy[J]. Biol Reprod, 2021, 104(2): 252-254. DOI: 10.1093/biolre/ioaa220.
[5] Shen Y, Cui QY, Xiao L, et al. Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells[J]. J Perinat Med, 2024, 52(1): 41-49. DOI: 10.1515/jpm-2022-0565.
[6] Liang MM, Niu JM, Zhang L, et al. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia[J]. Placenta, 2016, 40: 52-59. DOI: 10.1016/j.placenta.2016.02.015.
[7] Yuki K, Vallon M, Ding J, et al. GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanism[J]. Development, 2024, 151(11): dev202794. DOI: 10.1242/dev.202794.
[8] 徐怡倩, 吴昊霖, 方星悦, 等. G蛋白偶联受体124生理及药理功能研究进展[J]. 海南医学院学报, 2022, 28(14): 1108-1113, 1120. DOI: 10.13210/j.cnki.jhmu.20210322.001.
[9] Xu YQ, Fang XY, Zhao ZQ, et al. GPR124 induces NLRP3 inflammasome-mediated pyroptosis in endothelial cells during ischemic injury[J]. Eur J Pharmacol, 2024, 962: 176228. DOI: 10.1016/j.ejphar.2023.176228.
[10] 谢幸, 孔北华, 段涛. 妇产科学[M]. 9版. 北京:人民卫生出版社, 2019: 83-84.
[11] 宋丹丹. 子痫前期患者HMGB1、ADMA水平变化及与螺旋动脉管壁厚度及管腔面积的相关性[J]. 中国计划生育学杂志, 2023, 31(3): 632-635. DOI: 10.3969/j.issn.1004-8189.2023.03.031.
[12] Shen Y, Lian Y, Xiao L, et al. GPR124 promotes trophoblast proliferation, migration, and invasion and inhibits trophoblast cell apoptosis and inflammation via JNK and P38 MAPK pathways[J]. J Cell Physiol, 2024, 239(8): e31298. DOI: 10.1002/jcp.31298.
[13] Posokhova E, Shukla A, Seaman S, et al. GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling[J]. Cell Rep, 2015, 10(2): 123-130. DOI: 10.1016/j.celrep.2014.12.020.
[14] Lan LH, Wang W, Huang Y, et al. Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases[J]. J Cell Biochem, 2019, 120(11): 18588-18598. DOI: 10.1002/jcb.29217.
[15] Cho C, Smallwood PM, Nathans J. Reck and Gpr124 are essential receptor cofactors for Wnt7a/Wnt7b-specific signaling in mammalian CNS angiogenesis and blood-brain barrier regulation[J]. Neuron, 2017, 95(5): 1056-1073.e5. DOI: 10.1016/j.neuron.2017.07.031.
[16] 唐跃东, 谢启亮, 汪兰曌, 等. 白蛋白对老年大鼠全脑缺血再灌注后G蛋白偶联受体124表达和血脑屏障的影响[J]. 老年医学与保健, 2022, 28(6): 1245-1251. DOI: 10.3969/j.issn.1008-8296.2022.06.017.
[17] Bisson C, Dautel S, Patel E, et al. Preeclampsia pathophysiology and adverse outcomes during pregnancy and postpartum[J]. Front Med, 2023, 10: 1144170. DOI: 10.3389/fmed.2023.1144170.
[18] Ghalehbandi S, Yuzugulen J, Pranjol MZI, et al. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF[J]. Eur J Pharmacol, 2023, 949: 175586. DOI: 10.1016/j.ejphar.2023.175586.
[19] Bayor F, Adu‐Bonsaffoh K, Antwi‐Boasiako C. Maternal serum angiopoietins levels in pre-eclampsia and pregnancy outcomes[J]. Health Science Reports, 2024, 7(1): e1806. DOI: 10.1002/hsr2.1806.
[20] Wolf A, Langmann T. Anti-VEGF-A/ANG2 combotherapy limits pathological angiogenesis in the eye: a replication study[J]. EMBO Mol Med, 2019, 11(5): e10362. DOI: 10.15252/emmm.201910362.
[21] Stepan H, Galindo A, Hund M, et al. Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction[J]. Ultrasound Obstet Gynecol, 2023, 61(2): 168-180. DOI: 10.1002/uog.26032.
[22] 韩钰静, 王晶, 任景珊, 等. 血清sFlt-1、PLGF与子痫前期发病及病情严重程度的关系[J]. 临床和实验医学杂志, 2024, 23(7): 738-741. DOI: 10.3969/j.issn.1671-4695.2024.07.017.
[23] Aggarwal R, Jain AK, Mittal P, et al. Association of pro- and anti-inflammatory cytokines in preeclampsia[J]. J Clin Lab Anal, 2019, 33(4): e22834. DOI: 10.1002/jcla.22834.
[24] Wang S, Liu YN, Liang Y, et al. Excessive immune activation and the correlation with decreased expression of PD-1 at the maternal-fetal interface in preeclampsia[J]. Reprod Sci, 2023, 30(1): 192-202. DOI: 10.1007/s43032-022-01003-z.
[25] Calderón-Zamora L, Ruiz-Hernandez A, Romero-Nava R, et al. Possible involvement of orphan receptors GPR88 and GPR124 in the development of hypertension in spontaneously hypertensive rat[J]. Clin Exp Hypertens, 2017, 39(6): 513-519. DOI: 10.1080/10641963.2016.1273949.