冠状动脉支架内再狭窄相关miRNA表达谱分析和功能研究

发布时间：2018-02-28 19:27

本文关键词： 冠心病支架内再狭窄 miRNA 靶基因生物信息学　出处：《青岛大学》2016年博士论文　论文类型：学位论文

【摘要】：背景Micro RNA(mi RNA)是一类在转录后水平调控基因表达的非编码RNA,目前发现它广泛参与了心血管疾病各个过程。支架内再狭窄(ISR)目前已经成为冠脉介入治疗术后有待解决的重大难题,现推测mi RNA可能在ISR中发挥重要作用。本研究将对mi RNA在ISR发病机制中的作用进行初步探讨。目的筛选出ISR患者特异性表达的mi RNA,分析其相对表达量与临床的相关性,初步探讨mi RNA及其靶基因在ISR中可能的作用机制。方法通过mi RNA基因芯片技术筛选ISR患者血浆mi RNA的表达谱差异,以筛选出与ISR相关的mi RNA;通过Real-time PCR对mi RNA的相对表达量与ISR进行相关性分析及验证,最终将筛选出特异性的mi RNA用作ISR高危人群的标记物;通过生物信息学技术对mi RNA靶基因进行预测,并对mi RNA的下游靶基因网络进行数据挖掘,构建ISR相关mi RNA-Gene-Network网络,探讨其在ISR中可能的作用机制。结果通过高通量mi RNA芯片检测,筛选获得了一批在ISR患者中差异表达的mi RNA,其中43个基因表达下调,10个基因表达上调。通过生物信息学方法及Real-time PCR对基因芯片结果进行了分析及验证,通过比较及ROC曲线分析,发现hsa-mi R-126可以作为冠心病患者ISR早期诊断的潜在分子标志物,血浆hsa-mi R-126水平下降倾向于发生ISR。通过生物信息学方法,预测了mi R-126的靶基因,构建了mi R-126及其靶基因的信号通路,并发现了16个潜在Gene靶点和24个潜在mi RNA靶点可能也参与了该信号网络,而这些潜在的靶点中也可能存在ISR的关键基因。结论本研究表明mi RNA在ISR发病中起重要作用,hsa-mi R-126下降可以作为冠心病患者支架术后容易发生ISR的早期诊断标志物。但hsa-mi R-126在ISR中的作用机制复杂,它可能通过调控多个途径中的靶基因来参与ISR的发生和发展过程。
[Abstract]:Background Micro RNA(mi is a kind of non-coding RNAs that regulate gene expression at post-transcriptional level. It has been found that it is widely involved in various processes of cardiovascular disease. Restenosis in stent has become a major problem to be solved after coronary intervention. It is speculated that mi RNA may play an important role in ISR. This study will explore the role of mi RNA in the pathogenesis of ISR. To explore the possible mechanism of mi RNA and its target gene in ISR. Methods the difference of expression profiles of mi RNA in plasma of ISR patients was screened by mi RNA gene chip technique. The relative expression of mi RNA and ISR were analyzed and verified by Real-time PCR. Finally, the specific mi RNA was used as marker of ISR high risk population. The target gene of mi RNA was predicted by bioinformatics, and the downstream target gene network of mi RNA was mined to construct the ISR related mi RNA-Gene-Network network. The possible mechanism of its role in ISR was discussed. The results were detected by high throughput mi RNA chip. A batch of differentially expressed miRNAs were obtained in patients with ISR. Among them, 43 genes were down-regulated and 10 genes were up-regulated. The microarray results were analyzed and verified by bioinformatics and Real-time PCR, and the results were analyzed by comparison and ROC curve analysis. It was found that hsa-mi R-126 could be used as a potential molecular marker for early diagnosis of ISR in patients with coronary heart disease, and that the decrease of plasma hsa-mi R-126 level tended to cause ISR.The target gene of miR-126 was predicted by bioinformatics, and the signal pathway of miR-126 and its target gene was constructed. 16 potential Gene targets and 24 potential mi RNA targets may also be involved in the signaling network. The key genes of ISR may also exist in these potential targets. Conclusion this study suggests that the decrease of mi RNA may play an important role in the pathogenesis of ISR. The decrease of hsa-mi R-126 may be used as an early diagnostic marker of ISR in patients with coronary heart disease. But the mechanism of hsa-mi R-126 in ISR is complicated. It may be involved in the genesis and development of ISR by regulating the target genes in multiple pathways.
【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4

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