胎盘组织肿瘤坏死因子-α基因表观遗传修饰与胎盘血肿患者发生早产相关性研究  

Correlation between epigenetic modification of TNF-αgene in placental tissuesand the occurrence of preterm birth in patients with placental hematoma

作　　者：杨标 李慧 吴盈 林静 张琼霞 胡春霞 YANG Biao;LI Hui;WU Ying;LIN Jing;ZHANG Qiongxia;HU Chunxia(Department of Obstetrics,the First Affiliated Hospital of Hainan Medical University,Haikou 570100,China)

机构地区：[1]海南医科大学第一附属医院产科,海南海口570100

出　　处：《陕西医学杂志》2025年第2期263-267,共5页Shaanxi Medical Journal

基　　金：海南省重点研发计划项目(ZDYF2019162)。

摘　　要：目的:探究胎盘组织肿瘤坏死因子-α(TNF-α)基因表观遗传修饰与胎盘血肿患者发生早产的相关性。方法:选取34例胎盘血肿合并早产患者(血肿早产组)、23例胎盘血肿未合并早产患者(血肿足月组)和30例足月分娩的健康孕妇(对照组)。收集孕妇胎盘组织,分别采用免疫组织化学染色法检测TNF-α蛋白表达,甲基化特异性聚合酶链式反应检测TNF-α基因启动子区域甲基化状态,RT-qPCR法检测TNF-αmRNA表达,ELISA法检测TNF-α蛋白含量,染色质免疫共沉淀测序分析TNF-α基因启动子区域组蛋白H3K4me3、H3K27me3、H3K4me1和H3K27ac的修饰程度。结果:血肿早产组孕周短于血肿足月组和对照组(均P<0.05)。免疫组化染色结果显示,血肿早产组胎盘组织可见大片棕黄色,细胞质中有大量棕黄色颗粒;血肿足月组有少量黄色区域,颜色较浅;对照组基本无黄色颗粒,仅部分细胞质中有黄色。血肿早产组和血肿足月组患者TNF-α基因启动子区域完全甲基化占比低于对照组,TNF-α基因启动子区域未甲基化占比高于对照组(均P<0.05)。血肿早产组、血肿足月组和对照组胎盘组织TNF-αmRNA及蛋白表达水平依次递减(均P<0.05)。血肿早产组、血肿足月组和对照组胎盘组织TNF-α基因启动子区域组蛋白H3K4me3的修饰程度逐渐升高,H3K4me1和H3K27ac的修饰程度逐渐降低(均P<0.05)。与血肿早产组和血肿足月组比较,对照组胎盘组织TNF-α基因启动子区域组蛋白H3K27me3修饰程度升高(均P<0.05)。结论:胎盘血肿患者胎盘组织TNF-α高表达,TNF-α基因甲基化和组蛋白修饰可能与孕妇胎盘血肿和早产有关。Objective:To investigate the correlation between epigenetic modifications of the tumor necrosis factor-α(TNF-α)gene in placental tissue and the occurrence of preterm birth in patients with placental hematoma.Methods:A total of 34 patients with placental hematoma and preterm birth(hematoma preterm group),23 patients with placental hematoma without preterm birth(hematoma term group),and 30 healthy pregnant women without preterm birth(control group)were selected.Placental tissues were collected from the pregnant women.Immunohistochemical staining was used to detect TNF-αprotein expression.Methylation-specific polymerase chain reaction was used to assess the methylation status of the TNF-αgene promoter region.RT-qPCR was used to detect TNF-αmRNA expression.ELISA was used to measure TNF-αprotein content,and chromatin immunoprecipitation sequencing was used to analyze the modification levels of histones H3K4me3,H3K27me3,H3K4me1 and H3K27ac in the TNF-αgene promoter region.Results:The gestational age in the hematoma preterm group was shorter than in the hematoma term group and the control group(all P<0.05).Immunohistochemical staining results showed that the placentas from the hematoma preterm group had large areas of brown-yellow color with numerous brown-yellow granules in the cytoplasm;the hematoma term group had a few yellow areas with lighter color;the control group had almost no yellow granules,with only some yellow in the cytoplasm.The proportion of fully methylated TNF-αgene promoter regions in the hematoma preterm and hematoma term groups was lower than in the control group,while the proportion of unmethylated TNF-αgene promoter regions was higher than in the control group(all P<0.05).TNF-αmRNA and protein expression levels in placental tissues were decreased in the order of hematoma preterm group,hematoma term group,and control group(all P<0.05).The modification levels of histone H3K4me3 in the TNF-αgene promoter region were gradually increased,while the modification levels of H3K4me1 and H3K27ac we

关 键 词：胎盘血肿 肿瘤坏死因子-α 早产 表观遗传修饰 DNA甲基化 组蛋白修饰 

分 类 号：R714.2[医药卫生—妇产科学]