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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2008, Vol. 28 Issue (1): 1-7    
论文     
致心律失常型右室心肌病引起的心力衰竭分子标志物的筛选
魏英杰 胡盛寿 黄洁 黄银霞 李君 张晓玲 李望 张浩 唐跃
中国医学科学院阜外心血管病医院
Screening of Molecular Biomarkers Associated with Heart Failure Derived from Arrhythmogenic Right Ventricular Cardiomyopathy
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摘要:

目的:筛选致心律失常型右室心肌病引起心力衰竭的分子标志物。方法:从本院的心脏病组织库中挑选5例病理诊断明确和各方面资料比较齐全的致心律失常型右室心肌病引起心力衰竭的心脏病标本(来源于心脏移植的受体),与年龄、性别和种族等因素相匹配的正常对照心脏组织(来源于心脏移植的供体)进行全基因组表达芯片的比较研究。提取致心律失常型右室心肌病的左心室组织RNA,同时提取正常对照心脏相应部位的RNA。应用晶芯人类全基因组寡核苷酸微阵列基因表达谱芯片(含有人类基因35,000个),筛选致心律失常型右室心肌病引起的心力衰竭基因表达谱的改变。应用实时定量荧光反转录聚合酶链式反应(real-time RT-PCR)验证致心律失常型右室心肌病引起的心力衰竭基因表达改变的真实性和准确性。 结果:应用基因表达芯片研究方法共筛选出78个差异表达基因,其中有35个基因在致心律失常型右室心肌病引起的心力衰竭中表达升高,而另有43个基因表达降低。其中变化较多的基因属于与代谢相关的基因。对其中36个差异表达基因应用real-time RT-PCR的方法进行了验证,差异表达基因的准确性在75%,并首次报告了心钠素在致心律失常型右室心肌病引起的心力衰竭中表达明显升高。结论:本研究在世界上首次应用基因表达芯片的方法,观察了致心律失常型右室心肌病引起的心力衰竭基因表达谱的改变,为致心律失常型右室心肌病引起的心力衰竭分子机制的阐明和寻找疾病特异的分子标志物,以用于鉴别诊断、判断病情和预后及指导个性化治疗奠定了基础。

Abstract:

Objective: To sieve molecular biomarkers associated with heart failure derived from arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: We performed comparative gene microarray analysis using Individual left ventricular myocardial samples from 5 patients with heart failure resulting from ARVC undergoing transplantation and 5 matched samples from normal adult heart. The accuracy rate of the differentially expressed genes obtained by gene microarray was further verified by quantitative real time RT-PCR. Results: We identified 83 genes (from a total of 35,000) that were differentially expressed in diseased hearts versus normal hearts. Among them thirty-seven genes were up-regulated and forty-eight genes were down-regulated in ARVC hearts compared with the normal hearts. Changes of gene expressions were most prominently observed in those belonging to the "metabolism" category. Eighty percent of the selected 30 differentially expressed genes from microarray analysis were confirmed by quantitative real time RT-PCR. We reported the highly expressed level of atrial natriuratic peptide (ANP) in ARVC hearts that was confirmed by quantitative real time RT-PCR and immunohistochemistry. Conclusion: We identified, for the first time to our knowledge, the altered expressed genes in ARVC hearts compared with the matched normal hearts. Our results are the base to further study the molecular mechanism and identify diseased-specific molecular biomarkers in heart failure derived from ARVC.

收稿日期: 2007-07-05 出版日期: 2008-01-25
通讯作者: 胡盛寿   
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引用本文:

魏英杰,胡盛寿,黄洁,黄银霞,李君,张晓玲,李望,张浩,唐跃. 致心律失常型右室心肌病引起的心力衰竭分子标志物的筛选[J]. 中国生物工程杂志, 2008, 28(1): 1-7.

. Screening of Molecular Biomarkers Associated with Heart Failure Derived from Arrhythmogenic Right Ventricular Cardiomyopathy. China Biotechnology, 2008, 28(1): 1-7.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2008/V28/I1/1

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