慢性子宫内膜炎口服抗生素治疗前后的转录组测序研究  

Transcriptome sequencing study of chronic endometritis before and after oral antibiotic treatment

作　　者：袁莹 陈雪梅 刘容菊 何红梅 王静怡 邹志玲 周丽玲 陈博 李青洋 潘瑞华 蔡昭炜 YUAN Ying;CHEN Xue-mei;LIU Rong-ju;HE Hong-mei;WANG Jing-yi;ZOU Zhi-ling;ZHOU Li-ling;CHEN Bo;LI Qing-yang;PAN Rui-hua;CAI Zhao-wei(Guangdong Medical University,Zhanjiang 524001;Reproductive Medicine Center,Dongguan Songshan Lake Central Hospital,Dongguan523326)

机构地区：[1]广东医科大学,湛江524001 [2]东莞市松山湖中心医院生殖中心,东莞523326

出　　处：《生殖医学杂志》2023年第1期68-78,共11页Journal of Reproductive Medicine

基　　金：东莞市社会科技发展(重点)项目(201950715024177)。

摘　　要：目的探究慢性子宫内膜炎(CE)患者口服抗生素治疗前后子宫内膜的基因表达变化。方法选取2019年1月至2021年10月就诊于东莞市松山湖中心医院生殖中心被诊断为CE经口服盐酸多西环素片与甲硝唑片进行治疗后转阴的25例患者为研究对象,收集患者治疗前后的子宫内膜,分别进行转录组测序,采用DESeq2 v1.22.1软件进行基因表达水平分析和差异基因筛选,并对差异表达基因进行KEGG(Kyoto Encyclopedia of Genes and Genomes)分析。结果CE经口服抗生素治疗后1疗程转阴率80.0%,2疗程转阴率96.0%,3疗程转阴率100%。共鉴定70492个转录本,筛选出29510个差异表达基因,其中上调11519个,下调17991个。KEGG分析表明上调表达的基因主要富集到多种疾病相关的途径,而下调表达的基因富集到PI3K-Akt信号途径、MAPK信号途径、鞘脂类信号途径和甲状腺激素信号途径等。将至少在14例CE患者中表达模式一致的差异基因划分为显著差异表达基因,共筛选出38个显著差异表达基因,其中胚胎着床调控基因RASD 1的表达水平在治疗后显著提高(P<0.001),与炎症反应相关的GPX 3、MMP 7和NTN 4的表达水平在治疗后显著下调(P<0.001)。结论抗生素治疗CE前后子宫内膜基因表达存在显著差异,本研究为CE的发病机制与诊断提供了新的研究方向。Objective:To explore the changes of gene expression in endometrium of patients with chronic endometritis(CE)before and after oral antibiotics treatment.Methods:A total of twenty-five patients who were diagnosed as CE and turned negative after treated by oral doxycycline hydrochloride tablet and metronidazole tablet in the Reproductive Medicine Center of Dongguan Songshan Lake Central Hospital from October 2019 to October 2021 were selected as the objects.The endometrium of the patients before and after treatment were collected for transcriptome sequencing.The gene expression level and differential genes were analyzed by DESeq2v1.22.1 software,and the differentially expressed genes were analyzed by KEGG(Kyoto Encyclopedia of Genes and Genomes).Results:The negative conversion rate of CE after oral antibiotic treatment was 80%in the first course,96.0%in the second course and 100%in the third course.A total of 70492 transcripts were identified.A total of 29510 differentially expressed genes were screened,including 11519 up-regulated and 17991 down-regulated.KEGG analysis showed that the up-regulated genes were mainly enriched in a variety of disease-related pathways,while the down-regulated genes were enriched in PI3K-Akt signal pathway,MAPK signal pathway,sphingolipid signal pathway and thyroid hormone signal pathway.Due to the huge differences between individuals,the differentially expressed genes with consistent expression patterns in at least 14 patients with CE were classified as significantly differentially expressed genes.On this basis,38 significantly differentially expressed genes were screened out,among which the expression level of RASD1,a gene regulating embryo implantation,was significantly increased after treatment(P<0.001).However,the expression levels of GPX3,MMP7 and NTN4 related to inflammation were significantly down-regulated after treatment(P<0.001).Conclusions:Abundant differentially expressed genes are observed before and after the treatment of CE,and this study support a new insight into the p

关 键 词：慢性子宫内膜炎 抗生素 转录组测序 RASD1 炎症 

分 类 号：R711.32[医药卫生—妇产科学]