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出 处:《天津医药》2013年第5期455-458,共4页Tianjin Medical Journal
基 金:国家自然科学基金资助项目(项目编号:30940066)
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。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 model was established by modified cuff sleeve method. The experimental animals were divided into syngeneie control group, xenogeneie group (24 hours) and xenogeneic group (ar- resting). Total of 579 miRNAs were detected by miRNA array and significantly differential expressed miRNAs were filtrated in the cardiac xenotransplantation rejection. MiR-146a and miR-451 in three groups, which were obviously changed during xenotransplantation, were analyzed by TaqMan~ miRNA Assays, verifying the results of miRNA array. Results There were 24 miRNAs (11 down-regulated miRNAs and 13 up.--regulated miRNAs) showed significant differences between xenogeneic group (24hours) and control group. A total of 25 miRNAs were found significantly different between xenogeneie group (arrest- ing) and control group, including 12 down-regulated miRNAs and 13 up-regulated miRNAs. The expression level of MiR-146a was significantly higher in xenogeneic group than that of syngeneic control group. The expression level of miR-451 was significantly lower in xenogeneic group than that of syngeneic control group (F=15.530 and 13431.6, P 〈 0.05). Conclusion There are muhiple significantly expressed miRNAs in mouse to rat cardiac xenotransplantation rejection (high expression of miR-146a and low expression of miR-451), suggesting an important role in regulating the cardiac xenotrans- plantation.
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