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目的探讨重度子痫前期和正常妊娠胎盘组织差异微小RNA(miRNA)及其靶基因在重度子痫前期致病机制中的作用。方法选择剖宫产分娩的重度子痫前期患者和正常妊娠孕妇各5例,应用芯片技术分别检测重度子痫前期和正常妊娠胎盘组织miRNA和mRNA的表达情况,并对差异miRNA和mRNA表达谱进行整合分析,确定在重度子痫前期胎盘组织中差异表达的miRNA的靶基因,并应用生物分子功能注释系统V3.0(MAS V3.0)明确靶基因的生物学功能。结果通过miRNA表达谱芯片筛选出81个差异表达的miRNA,其中80个表达上调,1个表达下调;通过mRNA表达谱芯片筛选出660个差异表达基因,其中256个表达上调,404个表达下调。由于miRNA对其靶基因的负调控作用,通过数据库分析预测及整合分析,得到了56个miRNA靶基因、142个miRNA-靶基因对。这些靶基因涉及离子转运、细胞粘附、血压调节、氧化还原、缺氧反应、炎症反应和信号转导等多方面功能,以及紧密连接、细胞周期、Wnt信号通路、MAPK信号通路、神经活性配体-受体相互作用等多个信号传导通路。结论重度子痫前期患者胎盘组织中差异表达的miRNA及其调控的靶基因可能与重度子痫前期的病及病理生理过程相关。
Objective To investigate the role of differential microRNAs (miRNAs) and their target genes in the pathogenesis of severe preeclampsia in severe preeclampsia and normal pregnancy. Methods Five patients with severe preeclampsia and normal pregnant women delivered by cesarean section were selected. The expression of miRNAs and miRNAs in placenta of severe preeclampsia and normal pregnancy were detected by microarray technique. The differential miRNA and mRNA expression profiles were determined The target genes of miRNAs differentially expressed in placenta of severe preeclampsia were determined by integration analysis. The biological function of target genes was clarified by using V3.0 (MAS V3.0). Results Eighty-one differentially expressed miRNAs were screened by miRNA microarrays, of which 80 were up-regulated and one was down-regulated. A total of 660 differentially expressed genes were screened by mRNA expression profiling, of which 256 were up-regulated and 404 were down-regulated. Due to the negative regulatory effect of miRNA on its target genes, 56 miRNA target genes and 142 miRNA-target gene pairs were obtained through database analysis and integration analysis. These target genes are involved in various functions such as ion transport, cell adhesion, blood pressure regulation, redox, hypoxia, inflammation and signal transduction, as well as tight junctions, cell cycle, Wnt signaling pathway, MAPK signaling pathway, neural activity distribution Body-receptor interactions and other signal transduction pathways. Conclusions The differentially expressed miRNAs and their regulatory targets in severe preeclampsia may be related to the disease and pathophysiological processes in severe preeclampsia.