同济大学学报(医学版)2025,Vol.46Issue(6):811-818,8.DOI:10.12289/j.issn.2097-4345.25395
脂多糖诱导早产大鼠宫颈重塑障碍的转录组学分析
Transcriptomic analysis of lipopolysaccharide-induced cervical remodeling dysfunction in a rat model of preterm birth
摘要
Abstract
Objective To analyze the gene expression changes and the potential mechanisms in cervical tissue of a lipopolysaccharide(LPS)-induced rat model of preterm birth using transcriptomic sequencing.Methods Transcriptome sequencing was performed on cervical tissues from pregnant rats administered with intraperitoneal LPS or phosphate buffered saline(PBS)injections.Differentially-expressed genes(DEGs)were analyzed through gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses to identify key genes associated with cervical remodeling,inflammation,extracellular matrix,and the bradykinin system.The genes were validated with quantitative reverse transcription polymerase chain reaction(qRT-PCR).Results All LPS-treated rats experienced preterm birth(100%vs 0%,P=0.000 5)with significantly shortened gestation periods[(18.08±0.38)days vs(21.92±0.58)days,P<0.000 1].Transcriptomic analysis revealed 892 upregulated and 725 downregulated genes in the LPS group.The GO analysis showed that DEGs were enriched in immune response,extracellular matrix and chemokine activity pathways.The KEGG analysis indicated that inflammatory responses and the bradykinin system may disrupt extracellular matrix stability,leading to disorders associated cervical insufficiency and preterm birth.The QRT-PCR validation of key cervical remodeling genes confirmed upregulation of interleukin(IL)-6,tumor necrosis factor(TNF)-α,collagen type 3 α1(COL3A1),lysyl oxidase(LOX),matrix metalloproteinase 9(MMP9),prostaglandin endoperoxide synthase 2(PTGS2),kininogen 1(KNG1),and membrane metalloendopeptidase(MME)in the LPS group,consistent with transcriptomic findings.Conclusion LPS triggers preterm birth by activating inflammatory responses and the bradykinin system,synergistically regulating the PTGS2/PGE2 pathway and cervical remodeling-related genes,ultimately causing extracellular matrix dysfunction and cervical insufficiency.关键词
早产/宫颈重塑/转录组学/脂多糖/缓激肽/炎症/大鼠Key words
preterm birth/cervical remodeling/transcriptomics/lipopolysaccharide/bradykinin/inflammation/rat分类
医药卫生引用本文复制引用
高诣婕,孟璐璐,冯晓琬,王子诺,汝萍,刘云,王凌,倪晓田,刘铭..脂多糖诱导早产大鼠宫颈重塑障碍的转录组学分析[J].同济大学学报(医学版),2025,46(6):811-818,8.基金项目
上海市浦东新区卫生系统重点专科建设项目(PWZzk2022-11) (PWZzk2022-11)
上海市浦东新区高峰高原学科建设临床医学新质专科(专病)项目(2024-PWXZ-15) (专病)