慢性缺氧改变外周血转录组模式

王婷婷; 邢珺月; 张立靖; 张浩

doi:10.24920/003598

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慢性缺氧改变外周血转录组模式

中国医学科学杂志（英文版） 2020年35卷第1期页码：54-64

Original Article | Updated：2024-04-10

- 慢性缺氧改变外周血转录组模式
- Affiliations：
  
  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
- Author bio：
  
  * E-mail: drzhanghao@yahoo.com
- Funds：
  
  This study was supported by the National Science Fund for Distinguished Young Scholars(81525002);This study was supported by the National Science Fund for Distinguished Young Scholars(2016-2020)
- DOI：10.24920/003598
  中图分类号：
- 收稿日期：2019-05-20，
  
  网络出版日期：2020-03-31，
  
  纸质出版日期：2020-01-20
- Accepted：
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王婷婷, 邢珺月, 张立靖, 等. 慢性缺氧改变外周血转录组模式[J]. 中国医学科学杂志（英文版）, 2020,35(1):54-64.

Wang Tingting, Xing Junyue, Zhang Lijing, et al. Transcriptional Profile Alteration of Peripheral Blood in Chronic Hypoxia[J]. Chinese medical sciences journal, 2020, 35(1): 54-64.
王婷婷, 邢珺月, 张立靖, 等. 慢性缺氧改变外周血转录组模式[J]. 中国医学科学杂志（英文版）, 2020,35(1):54-64. DOI： 10.24920/003598.

Wang Tingting, Xing Junyue, Zhang Lijing, et al. Transcriptional Profile Alteration of Peripheral Blood in Chronic Hypoxia[J]. Chinese medical sciences journal, 2020, 35(1): 54-64. DOI： 10.24920/003598.

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

=6）分别暴露于低氧（10%O

）或常氧（21%O

）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（

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。

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 (

=6 per group) were either exposed to hypoxia (10% O

) or normoxia (21% O

) 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

-value (padj

0.05).

Results

Compared with the control group

the body weight of the rats in the hypoxia group was significantly lowered (

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.

关键词

Keywords

references

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