大鼠自体移植静脉差异表达microRNA及其生物信息学分析  

Differentially expressed microRNAs in rat autologous vein graft and their bioinformatics analysis

作　　者：万树威 李震[1] 曹辉[1] WAN Shuwei;LI Zhen;CAO Hui(Department of Endovascular Surgery,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院腔内血管外科

出　　处：《中国普通外科杂志》2019年第12期1490-1496,共7页China Journal of General Surgery

基　　金：国家自然科学基金资助项目（81600377）

摘　　要：目的:通过分析大鼠自体移植静脉microRNA(miRNA)表达谱,探讨miRNA对移植静脉内膜增生的调控机制。方法:将SD大鼠自体颈外静脉移植到肾下腹主动脉制作静脉移植模型,分别术后3、14d取移植静脉,以正常SD大鼠颈外静脉为对照,提取总RNA后用高通量测序技术检测miRNA表达谱,筛选差异表达miRNA并预测其靶基因,进行靶基因的GO富集分析和KEGG富集分析。结果:与正常静脉比较,术后14d的移植静脉差异表达miRNA总数为265,其中表达上调的miRNA有183个,表达下调的miRNA有82个;术后14d与术后3d的移植静脉间比较,差异表达的miRNA总数158,其中表达上调的miRNA有94个,表达下调的miRNA有64个。miRNA靶基因GO功能分析显示,富集的基因主要参与了DNA转录过程的调节、细胞间信号转导的调控和蛋白质磷酸化过程的调节;KEGG通路分析显示,富集的信号通路主要有MAPK信号通路、cAMP信号通路、Wnt信号通路、紧密连接、cGMP-PKG信号通路。结论:miRNA通过复杂的调控网络参与移植静脉内膜增生的生物学过程。所发现的miRNA及其调控网络可能为移植静脉内膜增生的机制研究与干预提供参考。Objective: To investigate the regulatory mechanism of miRNAs on intimal hyperplasia of the vein graft through analyzing the expression profile of micro RNAs(miRNAs) of autologous vein graft in rats.Methods: The rat vein graft models were established by grafting the autologous external jugular vein into the infrarenal abdominal aorta. The vein grafts were harvested on postoperative day(POD) 3 and 14, using the normal rat external jugular veins as control, and then, the miRNA expression profiles were determined by highthroughput sequencing after total RNA extraction, the differentially expressed miRNAs were screened out and their target genes were estimated. Finally, GO enrichment analysis and KEGG pathway analysis of the target genes were performed.Results: Compared with the normal vein, the total number of differentially expressed in the vein graft miRNAs on POD 14 was 265, in which, 183 miRNAs were up-regulated and 82 miRNAs were down-regulated. There were 158 differentially expressed miRNAs between the vein graft on POD 14 and POD 3, including 94 up-regulated miRNAs and down-regulated 64 miRNAs. The GO analysis of the target genes of the miRNAs showed that the enriched genes were mainly involved in the regulation of DNA transcription, the regulation of intercellular signal transduction and the regulation of protein phosphorylation. The KEGG pathway analysis showed that the enriched pathways were MAPK signaling pathway, c AMP signaling pathway, Wnt signaling pathway, tight junction and cGMP-PKG signaling pathway.Conclusion: Mi RNAs participate in the biological process of intimal hyperplasia of the vein graft through complex regulatory networks. The discovered miRNA and their regulatory networks may provide the reference framework for investigating the mechanism of intimal hyperplasia of the vein graft and its interventions.

关 键 词：血管移植术 静脉 血管内膜 微RNAS 计算生物学 

分 类 号：R654.3[医药卫生—外科学]