天津医药

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鼠异种心脏移植miRNA表达谱分析*

李川,戚峰,李富新,刘彤   

  1. 天津医科大学总医院
  • 收稿日期:2012-10-12 修回日期:2012-12-19 出版日期:2013-05-15 发布日期:2013-05-15
  • 通讯作者: 戚峰

LI CHUAN1,QI FENG1,LI FU XIN1,LIU TONG2   

  1. 1. Department of General Surgery, General Hospital of Tianjin Medical University
    2. Department of General Surgery, General Hospital of Tianjin Medical University,
  • Received:2012-10-12 Revised:2012-12-19 Published:2013-05-15 Online:2013-05-15
  • Contact: QI FENG

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摘要：

【摘要】 目的  研究小鼠-大鼠异种异位心脏移植后供心miRNA表达谱的变化,为有效控制异种移植排斥反应奠定实验基础。方法 采用改良Cuff袖套法建立小鼠-大鼠异位心脏移植模型,分为同系对照组、异种24h组和异种停跳组。通过miRNA芯片杂交筛选出异种心脏移植排斥反应中显著差异表达的miRNA,选取芯片结果中差异表达显著的miR-146a和miR-451进行相对定量研究,通过TaqMan miRNA Assays技术验证芯片结果。结果  异种24h组与同系对照组比较有24个miRNA差异表达显著,其中11个下调,13个上调。异种停跳组与同系对照组比较有25个miRNA差异表达显著,其中12个下调,13个上调。异种组的miR-146a表达水平高于同系对照组,miR-451表达水平低于同系对照组(F分别为15.530、13431.6,均P<0.05)。结论  在小鼠-大鼠异种心脏移植排斥反应中出现多个miRNA显著差异表达,其中miR-146a高表达,miR-451低表达,提示miRNA在异种心脏移植排斥反应中发挥着重要的调控作用。 

关键词: 心脏移植, 移植, 异种, 微RNAs, 芯片分析技术, 基因表达谱, 排斥反应

Abstract: Objective   To detect the miRNA expression profiles of the donor heart after the heterotopic mouse-rat cardiac xenotransplantation and provide the experimental evidences for effective regulation of xenotransplantation rejection. Methods   The heterotopic cardiac mouse-rat xenotransplantation models were established by modified cuff sleeve method. The experimental animals were divided into syngeneic control group, xenogeneic group (24 hours) and xenogeneic group (arresting). Total of 579 miRNAs were detected by miRNA array and significantly differential expressed miRNAs in the cardiac xenotransplantation rejection were filtrated. MiR-146a and miR-451 in the three groups, which were obviously changed during xenotransplantation, were analysis by TaqMan? miRNA Assays, verifying the results of miRNA array. Results   There were 11 down-regulated miRNAs and 13 up-regulated miRNAs among the total 24 significantly differential expressed miRNAs found in xenogeneic (24hours) group comparing with control group. There were 12 down-regulated miRNAs and 13 up-regulated miRNAs among the total 25 significantly differential expressed miRNAs found in xenogeneic (arresting) group comparing with control group. MiR-146a and miR-451 in the three groups were obviously changed following xenotransplantation comparing with control group（respectively F =15.530,1.343, all P<0.05）and the results were accordant with the results of miRNA array. Conclusions   It is demonstrated that there are many significantly differential expressed miRNAs in xenotransplantation rejection. Simultaneous high expression of miR-146a and low expression of miR-451 in mouse-rat cardiac xenotransplantation rejection reveal the relevance to the regulation of immune response and inflammation. The miRNA is proposed to play an important role in regulating the cardiac xenotransplantation.

Key words: heart transplantation, transplantation, heterologous, microRNAs, microchip analytical procedures, gene expression profiling, allograft rejection