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第44卷第1期 南京医科大学学报(自然科学版)
2024年1月 Journal of Nanjing Medical University(Natural Sciences) · 17 ·
·基础研究·
妊娠期糖尿病胎盘滋养细胞铁死亡超微结构及铁死亡相关基
因ACSL4、GPX4的表达
曹晓蓉 ,林倩楠 ,王慧艳 ,佘广彤 ,周文柏 ,夏丹丹 1
1
1
1*
2
1
南京医科大学常州医学中心,常州市妇幼保健院产科,实验室,江苏 常州 213016
1 2
[摘 要] 目的:观察妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇胎盘滋养细胞超微结构,探讨铁死亡在GDM发生
发展中的作用。方法:选取2020年9月—2022年12月在常州妇幼保健院分娩的孕妇,孕24~28周行口服葡萄糖耐量试验。以
确诊GDM的孕产妇为研究对象,分为通过饮食治疗控制血糖满意组(G1组)、口服二甲双胍控制血糖组(G2组)、胰岛素控制血
糖组(G3组)、血糖控制不满意但拒用药组(G4组)各30例,正常健康孕妇为对照组(N组)。通过透射电镜观察各组胎盘滋养
细胞超微结构;普鲁士蓝染色检查胎盘铁沉积情况;免疫组化检测胎盘长链脂酰辅酶 A 合成酶 4(acyl⁃CoA synthetase long
chain family member 4,ACSL4)、谷胱甘肽过氧化物酶 4(glutathione peroxidase 4,GPX4)在合体滋养细胞层的定位和表达;
Western blot和qRT⁃PCR分别检测胎盘ACSL4、GPX4蛋白和mRNA转录水平。结果:透射电镜下G1、G2、G3、G4组GDM产妇胎
盘均可见不同程度的线粒体形态学改变,其中G1、G2、G3组线粒体改变较轻,G4组见典型的铁死亡萎缩线粒体。普鲁士蓝染
色显示 5 组胎盘均见含铁颗粒,G1、G2、G3、G4 组胎盘中含铁颗粒较 N 组明显增多,G1、G2、G3 组胎盘中的含铁颗粒较 G4 组
明显减少。Western blot 结果显示,与 N 组相比,G1、G2、G3、G4 组产妇胎盘中 ACSL4 蛋白表达增加而 GPX4 蛋白表达下降,
qRT⁃PCR结果显示各组间ACSL4、GPX4的mRNA转录水平无显著性差异。结论:GDM孕妇胎盘滋养细胞中存在铁死亡,且与
病情严重程度和用药相关。GDM孕妇胎盘中ACSL4、GPX4表达异常,二甲双胍和胰岛素有改善胎盘滋养细胞铁死亡的作用。
[关键词] 铁死亡;妊娠期糖尿病;胎盘;合体滋养细胞
[中图分类号] R714 [文献标志码] A [文章编号] 1007⁃4368(2024)01⁃017⁃07
doi:10.7655/NYDXBNSN230601
Ultrastructure of ferroptosis and expression of ferroptosis⁃related ACSL4 and GPX4 genes
in placental trophoblasts of gestational diabetes mellitus
1 1 1* 1 2 1
CAO Xiaorong ,LIN Qiannan ,WANG Huiyan ,SHE Guangtong ,ZHOU Wenbo ,XIA Dandan
1 Changzhou Medical Center,Nanjing Medical University,Department of Obstetrics,Laboratory,Changzhou Maternal
2
and Child Health Care Hospital Affiliated to Nanjing Medical University,Changzhou 213016,China
[Abstract] Objective:To observe the ultrastructure of placental trophoblast cells of pregnant women with gestational diabetes
mellitus(GDM),and to investigate the role of ferroptosis in the occurrence and development of GDM. Methods:Pregnant women who
delivered at the Changzhou Maternal and Child Health Hospital from September 2020 to December 2022 were enrolled and underwent
an oral glucose tolerance test at 24-28 weeks of gestation. Pregnant women diagnosed with GDM were selected as the research subjects
and divided into four groups:diet⁃controlled glucose satisfaction group(G1 group),oral metformin⁃controlled glucose group(G2 group),
insulin⁃controlled glucose group(G3 group),and unsatisfactory glucose control but refused to use medication group(G4 group),each
with 30 cases. Normal healthy pregnant women were included as the control group(N group). The ultrastructure of placental
trophoblast cells in each group was observed by transmission electron microscopy. The placental iron deposition was detected by
Prussian blue staining. The localizations and expressions of Acyl⁃CoA synthetase long chain family member 4(ACSL4)and glutathione
peroxidase 4(GPX4)in the syncytiotrophoblast layer were detected by immunohistochemistry. The protein expressions and the mRNA
transcription levels of ACSL4 and GPX4 in the placenta were detected by Western blot and qRT⁃PCR,respectively. Results:Under
[基金项目] 常州市科技局应用基础项目(CJ20220117,CJ20220259)
∗
通信作者(Corresponding author),E⁃mail:huiyanwang@njmu.edu.cn