Chinese Medical Sciences Journal ›› 2020, Vol. 35 ›› Issue (1): 54-64.doi: 10.24920/003598

• 论著 • 上一篇    下一篇

慢性缺氧改变外周血转录组模式

王婷婷1,邢珺月1,张立靖3,张浩1,2,*()   

  1. 1中国医学科学院 北京协和医学院,国家心血管病中心 阜外心血管病医院, 心血管疾病国家重点实验室 北京 100037
    2海交通大学医学院附属上海儿童医学中心 上海市小儿先天性心脏病研究所,上海 200127
    3温州医科大学附属第二医院育英儿童医院儿童心脏中心 温州医科大学心脏发育与转化医学研究所,浙江,温州 325027
  • 收稿日期:2019-05-20 出版日期:2020-03-31 发布日期:2020-01-20
  • 通讯作者: 张浩 E-mail:drzhanghao@yahoo.com

Transcriptional Profile Alteration of Peripheral Blood in Chronic Hypoxia

Wang Tingting1,Xing Junyue1,Zhang Lijing3,Zhang Hao1,2,*()   

  1. 1State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
    2Heart Center and Shanghai Institution of Pediatric Congenital Heart Diseases, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    3Children's Heart Center, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
  • Received:2019-05-20 Published:2020-03-31 Online:2020-01-20
  • Contact: Zhang Hao E-mail:drzhanghao@yahoo.com

摘要:

目的 多种生理和病理状态都会伴随着慢性缺氧,例如紫绀型先天性心脏病(CCHD)。这种慢性缺氧可能会干扰基因的转录过程。然而,在缺氧条件下外周血转录组模式的改变尚无报道。故本工作旨在探讨慢性缺氧条件下,外周血转录组模式的变化。
方法 本研究使用慢性缺氧大鼠模型模拟CCHD患者的低氧状态。两组Sprague-Dawley大鼠(每组n=6)分别暴露于低氧(10%O2)或常氧(21%O2)条件下饲养3周。每周测量大鼠体重。缺氧处理结束后,采集两组大鼠外周血并提取总RNA进行RNA-Seq。经过质量评估后,通过Illumina Hiseq平台对文库进行测序。筛选差异表达基因(DEG),筛选条件为FDR(false discovery rate)<0.05且FC(fold change)>2。进行DEG的功能注释和聚类分析,并选取出padj(adjusted P-value)<0.05的条目。
结果 低氧组大鼠体重较对照组明显降低(P<0.01)。RNA-Seq结果表明:两组的转录组模式有显著差异。共鉴定出了872个差异表达的基因。在缺氧组中,共有803个基因下调,只有69个基因上调。对872个基因的功能富集分析表明:它们涉及了多个生物学过程,例如含卟啉的化合物代谢过程,血红蛋白复合物和氧转运蛋白活性等。
结论 我们的研究表明慢性缺氧大鼠模型外周血的转录组模式发生了显著改变。为进一步了解CCHD患者的生理和病理变化提供了理论基础和研究方向。

关键词: 慢性缺氧, RNA-Seq, 外周血, 紫绀型先天性心脏病

Abstract:

Objective Many physiological and pathological conditions, including cyanotic congenital heart diseases (CCHD), are accompanied by chronic hypoxia, which might interfere with the transcription process. However, the transcriptome profile in peripheral blood under hypoxia is still unidentified. The present work aimed to explore the transcriptional profile alteration of peripheral blood in chronic hypoxia.
Methods The present study used a chronic hypoxia rat model to simulate the hypoxic state of CCHD patients. Two groups of Sprague-Dawley rats (n=6 per group) were either exposed to hypoxia (10% O2) or normoxia (21% O2) for 3 weeks. Body weight was measured weekly. Peripheral blood was collected and total RNA was extracted for RNA-Seq at the end of the hypoxia treatment. After quality assessment, the library was sequenced by the Illumina Hiseq platform. The differentially expressed genes were screened (false discovery rate<0.05 and fold change>2). The functional annotation analysis and cluster analysis of differentially expressed genes were performed based on the adjusted P-value (padj<0.05).
Results Compared with the control group, the body weight of the rats in the hypoxia group was significantly lowered (P<0.01). RNA-Seq results showed that the transcriptome patterns of the two groups had significant differences. In total, 872 genes were identified as differentially expressed. Among all, 803 genes were down-regulated, while only 69 genes were up-regulated in the hypoxia group. The functional enrichment analysis of the 872 genes showed that multiple biological processes involved, such as porphyrin-containing compound metabolic process, hemoglobin complex and oxygen transporter activity.
Conclusions Our study demonstrated the transcriptional profile alteration in peripheral blood of chronic hypoxia rat model. This study provided basic data and directions to further understand the physiological and pathological changes in patients with CCHD.

Key words: chronic hypoxia, RNA-Seq, peripheral blood, cyanotic congenital heart diseases

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