铁死亡在子痫前期发病过程中的作用及机制研究  

Study on the role and mechanism of ferroptosis in the pathogenesis of preeclampsia

作　　者：何欣[1] 谢成茂 赵蓉[3] HE Xin;XIE Chengmao;ZHAO Rong(Department of Radiology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University Beijing Maternal and Child Health Care Hospital,Beijing 100026,China;Department of Gynaecology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University Beijing Maternal and Child Health Care Hospital,Beijing 100026,China;Department of Obstetrical,Beijing Obstetrics and Gynecology Hospital,Capital Medical University Beijing Maternal and Child Health Care Hospital,Beijing 100026,China)

机构地区：[1]首都医科大学附属北京妇产医院北京妇幼保健院放射科,北京100026 [2]首都医科大学附属北京妇产医院北京妇幼保健院妇科,北京100026 [3]首都医科大学附属北京妇产医院北京妇幼保健院产科,北京100026

出　　处：《中国医药导报》2025年第6期32-41,共10页China Medical Herald

摘　　要：目的应用生物信息学探索铁死亡在子痫前期发病过程中的潜在作用及机制。方法子痫前期相关表达谱数据集GSE75010、GSE10588来源于GEO数据库,其中GSE75010为训练集,而GSE10588为验证集。铁死亡相关基因信息从FerrDb数据库中下载。子痫前期铁死亡相关基因表达数据从GSE75010中提取。基因本体论及京都基因组百科全书富集分析明确差异基因参与的相关生物学功能、细胞组成及相关通路。采用SVM-RFE模型算法和LASSO算法筛选特征基因并建立逻辑回归模型;基因集富集分析明确特征基因富集的生物过程。基于特征基因构建竞争性内源性RNA(ceRNA)网络;使用GSE10588验证特征基因的表达情况。结果在GSE75010中获得了183个差异基因。差异基因主要参与“细胞对化学应激的反应”“对营养水平的反应”等功能;“神经退行性变的途径-多种疾病”“PI3K-Akt信号通路”等相关通路。LASSO及SVM-RFE联合分析共筛选出6个特征基因(ACSF2、ATG16L1、MYCN、PPARG、FGF21、RARRES2)。特征基因主要富集于嗅觉转导、氧化磷酸化、神经活动与受体相互作用、细胞因子受体相互作用及化学动力学等信号通路。ceRNA网络包含大量的信号通路及基因靶点。子痫前期胎盘组织中ACSF2、MYCN表达水平高于正常胎盘组织,RARRES2表达水平低于正常胎盘组织(P<0.05)。结论本研究应用生物信息学方法探究铁死亡在子痫前期发病过程中的作用及潜在机制,为临床探索子痫前期诊疗方法提供了新的理论基础。Objective To analysis the potential role and mechanism of ferroptosis in the pathogenesis of preeclampsia by using bioinformatics.Methods Preeclampsia related expression profile datasets GSE75010 and GSE10588 were derived from GEO database,in which GSE75010 was the training set and GSE10588 was the validation set.The gene information related to ferroptosis was downloaded from the FerrDb database.Gene expression data related to ferroptosis in preeclampsia were extracted from GSE75010.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses identified the relevant biological functions,cell composition,and pathways involved in differential genes;gene set enrichment analysis was used to definite the biological processes of characteristic gene enrichment.Competitive endogenous RNA(ceRNA)networks based on characteristic genes was constructed.GSE10588 was used to verify the expression of characteristic genes.Results A total of 183 differentially genes were obtained in the GSE75010.Differentially genes were mainly involved in functions such as“cell response to chemical stress”,“response to nutritional levels”;and related pathways such as“pathways of neurodegeneration-multiple diseases”,“PI3K-Akt signaling pathway”.LASSO and SVM-RFE combined analysis identified 6 characteristic genes(ACSF2,ATG16L1,MYCN,PPARG,FGF21,and RARRES2).Characteristic genes were mainly enriched in signaling pathways such as olfactory transduction,oxidative phosphorylation,neural activity and receptor interactions,cytokine receptor interactions,and chemical kinetics.The ceRNA network contained a large number of signaling pathways and gene targets.The expression levels of ACSF2 and MYCN in preeclampsia placenta were higher than those in normal placenta,and the expression level of RARRES2 was lower than that in normal placenta(P<0.05).Conclusion This study applied bioinformatics to explore the role and potential mechanisms of ferroptosis in the pathogenesis of preeclampsia,providing new theoretical basis for diagno

关 键 词：子痫前期 铁死亡 生物信息学分析 免疫调控 

分 类 号：R714.7[医药卫生—妇产科学]