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妊娠期糖尿病患者胎盘炎症增加:炎性小体NLRP-3和趋化因子清除诱饵受体D6的作用。

Placental inflammation is increased in gestational diabetes mellitus: The role of inflammasome NLRP-3 and chemokine scavenger decoy receptor D6.

作者信息

Onori Marianna, Beneduce Giuliana, Colella Filomena, Lucchetti Donatella, Policola Caterina, Arena Vincenzo, Sannino Fabio, Petrecca Alessandro, Pitocco Dario, Pontecorvi Alfredo, Sgambato Alessandro, Scambia Giovanni, Di Simone Nicoletta, Ghi Tullio, Tersigni Chiara

机构信息

Università Cattolica del Sacro Cuore, Rome, Italy.

Fondazione Policlinico Universitario A.Gemelli IRCCS, Rome, Italy.

出版信息

PLoS One. 2025 Jun 17;20(6):e0326087. doi: 10.1371/journal.pone.0326087. eCollection 2025.

DOI:10.1371/journal.pone.0326087
PMID:40526637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12173348/
Abstract

BACKGROUND

Gestational diabetes mellitus is characterized by low-grade systemic inflammation. Placental inflammation in gestation diabetes mellitus has not been extensively investigated yet.

OBJECTIVES

Aims of this study were to analyze: a) serum levels of Th-1 cytokines and D6-specific chemokines in women with gestation diabetes mellitus, compared to normal pregnant women; b) placental expression of the inflammasome NLR family pyrin domain containing 3 (NLRP-3) and the chemokines scavenger decoy D6 receptor.

METHODS

Serum samples collected between 24 and 28 weeks of pregnancy from singleton pregnancies with gestational diabetes mellitus and gestational age-matched normal pregnant women were analyzed by bead-based multiplex assays for chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 4 (CCL4), interferon gamma (IFN-γ), C-C motif chemokine ligand 11 (CCL11) and tumor necrosis factor alpha (TNF-α) levels. Placental samples from GDM and controls were analysed by immunohistochemistry and multiplex spatial immunofluorescence for protein expression of NLR family pyrin domain containing 3 (NLRP-3), interleukin-1 beta (IL-1β) and chemokines scavenger decoy D6 receptor.

RESULTS

GDM women (n = 25) showed higher serum levels of CCL-2 (p < 0.01), CCL-4 (p < 0.05) and IFN-γ (p < 0.05) compared to controls (n = 25). Placental expression of NLRP-3 was significantly higher in GDM women (n = 10) compared to controls (n = 7; p < 0.05) while only a trend of increase of IL-1β and D6 expression was observed in GDM compared to normal placentas.

CONCLUSIONS

GDM is characterized by higher serum levels of pro-inflammatory cytokines with consistent over-expression of the inflammasome NLRP-3 in placental tissues compared to normal pregnancy.

摘要

背景

妊娠期糖尿病的特征是低度全身性炎症。妊娠期糖尿病中的胎盘炎症尚未得到广泛研究。

目的

本研究的目的是分析:a)与正常孕妇相比,妊娠期糖尿病女性血清中Th-1细胞因子和D6特异性趋化因子的水平;b)含pyrin结构域的炎性小体NLR家族3(NLRP-3)和趋化因子清道夫诱饵D6受体在胎盘中的表达。

方法

通过基于磁珠的多重检测法分析妊娠24至28周期间从单胎妊娠的妊娠期糖尿病孕妇和孕龄匹配的正常孕妇采集的血清样本中趋化因子(C-C基序)配体2(CCL2)、趋化因子(C-C基序)配体4(CCL4)、干扰素γ(IFN-γ)、C-C基序趋化因子配体11(CCL11)和肿瘤坏死因子α(TNF-α)的水平。通过免疫组织化学和多重空间免疫荧光分析妊娠期糖尿病患者和对照组的胎盘样本中含pyrin结构域的NLR家族3(NLRP-3)、白细胞介素-1β(IL-1β)和趋化因子清道夫诱饵D6受体的蛋白表达。

结果

与对照组(n = 25)相比,妊娠期糖尿病女性(n = 25)血清中CCL-2(p < 0.01)、CCL-4(p < 0.05)和IFN-γ(p < 0.05)水平更高。与对照组(n = 7;p < 0.05)相比,妊娠期糖尿病女性(n = 10)胎盘中NLRP-3的表达显著更高,而与正常胎盘相比,妊娠期糖尿病中仅观察到IL-1β和D6表达有增加趋势。

结论

与正常妊娠相比,妊娠期糖尿病的特征是血清中促炎细胞因子水平较高,且胎盘组织中炎性小体NLRP-3持续过度表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/80f1e98f64fe/pone.0326087.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/8518d7760751/pone.0326087.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/bfc495a44f06/pone.0326087.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/bd1f4e260efa/pone.0326087.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/29bfc4606b57/pone.0326087.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/80f1e98f64fe/pone.0326087.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/8518d7760751/pone.0326087.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/bfc495a44f06/pone.0326087.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/bd1f4e260efa/pone.0326087.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/29bfc4606b57/pone.0326087.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af9/12173348/80f1e98f64fe/pone.0326087.g005.jpg

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