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

doi:10.3969/j.issn.1006-5725.2025.16.008

Abstract

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

CLC Number:

R714.25

Jingrui LI,Yaoyu SUO,Tian TIAN,Ping CAO,Zhifeng DONG,Nan JIANG,Huiping ZHANG,Kai WU,Qing SHI,Guizhong. LI. Study on the mechanism of PPARγ‐Targeted intervention in abnormal lipid Metabolism‐Induced dysfunction in placental trophoblast cells in preeclampsia and its clinical relevance[J]. The Journal of Practical Medicine, 2025, 41(16): 2489-2497.

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References 33

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组别	分娩年龄/岁	分娩孕周	收缩压/mmHg	舒张压/mmHg	BMI/（kg/m²）
正常妊娠组	29.70 ± 3.81	39.2 ± 1.1	113.00 ± 8.16	74.45 ± 8.14	25.33 ± 3.74
PE组	31.47 ± 4.46	36.8 ± 2.5	160.70 ± 11.85	102.70 ± 11.81	30.44 ± 6.20
t值	1.68	7.06	10.71	18.50	2.75
P值	> 0.05	< 0.01	< 0.001	< 0.001	< 0.01

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

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