实用医学杂志 ›› 2025, Vol. 41 ›› Issue (16): 2489-2497.doi: 10.3969/j.issn.1006-5725.2025.16.008

• 基础研究 • 上一篇    

基于过氧化物酶体增殖物激活受体γ干预对子痫前期胎盘滋养细胞脂质代谢异常致功能失调机制及临床关联

李婧睿1,锁耀宇2,田甜1,曹萍1,董治锋1,姜楠3,张慧萍4,吴凯2,石青,李桂忠1,2()   

  1. 1.宁夏医科大学,国家卫生健康委员会代谢性心血管疾病研究重点实验室,(宁夏 银川 750004 )
    2.宁夏医科大学,基础医学院,(宁夏 银川 750004 )
    3.中南大学湘雅医学院 (湖南 长沙 410013 )
    4.湖南省妇幼保健院医学遗传科(湖南长沙 410028);宁夏医科大学总医院5. 实验中心,6. 妇科 (宁夏 银川 750004 )
  • 收稿日期:2025-04-07 出版日期:2025-08-25 发布日期:2025-08-28
  • 通讯作者: 李桂忠 E-mail:lilylove36@163.com
  • 基金资助:
    国家自然科学基金面上项目(82371598);国家自然科学基金面上项目(82171682);宁夏回族自治区重点研发计划项目(2023BEG02074);宁夏回族自治区重点研发计划项目(2021BEG02028);宁夏回族自治区重点研发计划项目(2022BEG02054);湖南省卫生健康高层次人才重大科研专项(R2023120);宁夏医科大学校级科研重点项目(XZ2022005)

Study on the mechanism of PPARγ‐Targeted intervention in abnormal lipid Metabolism‐Induced dysfunction in placental trophoblast cells in preeclampsia and its clinical relevance

Jingrui LI1,Yaoyu SUO2,Tian TIAN1,Ping CAO1,Zhifeng DONG1,Nan JIANG3,Huiping ZHANG4,Kai WU2,Qing SHI,Guizhong. LI1,2()   

  1. Key Laboratory of Metabolic Cardiovascular Disease Research of National Health Commission,Ningxia Medical University,Yinchuan 750004,Ningxia,China
  • Received:2025-04-07 Online:2025-08-25 Published:2025-08-28
  • Contact: Guizhong. LI E-mail:lilylove36@163.com

摘要:

目的 探讨子痫前期(PE)患者胎盘脂质代谢异常与滋养细胞功能障碍的因果关系及PPARγ在缺氧环境下对滋养细胞功能的影响。 方法 收集2020年10月至2021年11月宁夏医科大学总医院30例PE患者及30例正常孕妇胎盘组织,检测脂质沉积情况;构建假手术组(Sham组)和减少子宫血流灌注组(Rupp组)大鼠子痫模型(n = 12,Sham组与Rupp组各6只);体外培养人滋养细胞HTR-8/SVneo,分组为正常对照组、缺氧组、缺氧+PPARγ激动剂(Rosiglitazone)组、缺氧+PPARγ拮抗剂(T0070907)组,通过RT-qPCR检测脂质代谢相关基因和转录因子(FASN、FABP4、PPARγ、LXRα)表达,Western blot检测PPARγ蛋白水平表达,划痕及Transwell实验评估细胞迁移侵袭能力。 结果 PE组胎盘脂质沉积显著高于对照组,Rupp模型鼠胎盘脂质沉积增加(P < 0.001);缺氧条件下滋养细胞FASN、FABP4表达上调(P < 0.001),PPARγ、LXRα表达下调(P < 0.001);PPARγ拮抗剂T0070907进一步加重缺氧对细胞功能的抑制(P < 0.001),且迁移侵袭能力显著降低(P < 0.001),进一步的si-PPARγ敲除实验显示,PPARγ敲除后加剧缺氧导致的细胞迁移和侵袭功能障碍,且这一现象无法被Rosiglitazone缓解。 结论 子痫前期胎盘脂质代谢异常与缺氧环境下PPARγ介导的脂质合成增加及代谢调控失衡密切相关,导致滋养细胞侵袭及迁移功能障碍。

关键词: 子痫前期, 脂质代谢, 滋养细胞, 过氧化物酶体增殖物激活受体, 磷酸化修饰

Abstract:

Objective To investigate the causal relationship between abnormal placental lipid metabolism and trophoblast dysfunction in patients with preeclampsia (PE), and to explore the regulatory effects of PPARγ on trophoblast function under hypoxic conditions. Methods Placental tissues were collected from 30 patients with PE and 30 individuals with normal pregnancies at the General Hospital of Ningxia Medical University between October 2020 and November 2021 for the analysis of lipid deposition. A rat model of PE was established, comprising a sham-operated (Sham) group and a reduced uterine perfusion pressure (Rupp) group, with six rats in each group (n = 12 total). Human trophoblast cells (HTR-8/SVneo) were cultured in vitro and randomly assigned to four experimental groups: normoxic control, hypoxia, hypoxia+PPARγ agonist (Rosiglitazone), and hypoxia+PPARγ antagonist (T0070907). The expression levels of lipid metabolism-related genes and transcription factors (FASN, FABP4, PPARγ, LXRα) were assessed using RT-qPCR. Western blotting was performed to determine the protein expression levels of PPARγ. Cell migration and invasion capacities were evaluated using scratch wound healing and Transwell assays, respectively. Results Placental lipid deposition in the PE group was significantly higher than that in the control group, particularly in the Rupp model mice (P < 0.001). Under hypoxic conditions, the expression levels of FASN and FABP4 were upregulated in trophoblast cells (P < 0.001), whereas the expression of PPARγ and LXRα was downregulated (P < 0.001). Furthermore, treatment with the PPARγ antagonist T0070907 exacerbated the inhibitory effects of hypoxia on cell function (P < 0.001), significantly reducing cell invasion and migration capacity (P < 0.001). Additional siRNA-mediated knockdown experiments confirmed that PPARγ deficiency further aggravated hypoxia-induced impairments in cell migration and invasion, and this detrimental effect could not be reversed by Rosiglitazone. Conclusions Abnormal placental lipid metabolism in PE is closely linked to PPARγ-mediated enhancement of lipid synthesis and metabolic dysregulation under hypoxic conditions, which may subsequently impair trophoblast invasion and migration.

Key words: preeclampsia, lipid metabolism, HTR-8/SVneo, PPAR, Post-translational phosphorylation

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