急性缺血性中风阴阳类证的血清转录组学特征分析

刘文琛; 李国铭; 何春华; 乔利军; 申昕; 程骁; 蔡业峰; 黄燕

doi:10.13422/j.cnki.syfjx.20190957

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急性缺血性中风阴阳类证的血清转录组学特征分析

临床 | 更新时间：2021-02-09

- 急性缺血性中风阴阳类证的血清转录组学特征分析
- Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke
- 中国实验方剂学杂志 2019年25卷第15期页码：122-130
- 作者机构：
  
  1.广州中医药大学　第二临床医学院，广州　 510120；
  2.广东省中医院，广州　 510120
- 作者简介：
  
  刘文琛，在读博士，住院医师，从事脑血管病的基础与临床研究，E-mail：wenchen20@foxmail.com
  黄燕，主任医师，教授，从事脑血管病的基础与临床研究，Tel：020-81887233-34530，E-mail：gdszyyhy@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81774042);广州市科技计划项目(201604020003)
- DOI：10.13422/j.cnki.syfjx.20190957
  中图分类号： R22; R24; Q342+ 3; C37
- 收稿日期：2019-01-02，
  
  网络出版日期：2019-01-17，
  
  纸质出版日期：2019-08-05
- 稿件说明：
移动端阅览
刘文琛, 李国铭, 何春华, 等. 急性缺血性中风阴阳类证的血清转录组学特征分析[J]. 中国实验方剂学杂志, 2019,25(15):122-130.

Wen-chen LIU, Guo-ming LI, Chun-hua HE, et al. Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 122-130.
刘文琛, 李国铭, 何春华, 等. 急性缺血性中风阴阳类证的血清转录组学特征分析[J]. 中国实验方剂学杂志, 2019,25(15):122-130. DOI： 10.13422/j.cnki.syfjx.20190957.

Wen-chen LIU, Guo-ming LI, Chun-hua HE, et al. Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 122-130. DOI： 10.13422/j.cnki.syfjx.20190957.

摘要

目的：

筛选急性缺血性中风阴类证、阳类证患者血清的差异表达长链非编码核糖核酸(lncRNA)，微小RNA(miRNA)，信使RNA(mRNA)，获取基因间调控关系，从转录组学层面探讨急性缺血性中风阴类证、阳类证形成的物质基础与生物学机制。

方法：

使用lncRNA，mRNA及miRNA芯片微阵列，分别检测急性缺血性中风阴类证、阳类证与非中风受试者(各10例)血清中lncRNA，miRNA与mRNA的表达情况，通过联合分析，筛选出阴类证、阳类证相关的差异表达谱。对获得的差异基因进行反义lncRNA与mRNA共表达分析、基因本体(GO)和京都基因与基因组百科全书(KEGG)功能通路分析，获取基因间调控关系，预测lncRNA的靶基因。对40例(阳类证10例，阴类证30例)样本中部分差异基因进行实时荧光定量聚合酶链式反应(Real-time PCR)验证。

结果：

227个lncRNA，54个mRNA，4个miRNA的表达与阳类证密切相关，394个lncRNA，206个mRNA的表达和阴类证密切相关。阳类证组中反义lncRNA RP11-647P12.1和RP11-677M14.2可能通过上调表达水平，分别调控神经元衍生神经营养因子(NDNF)和神经颗粒素(NRGN)的基因表达。通路富集显示，阴类证、阳类证之间转录组表达谱差异主要与血压调节、神经递质受体活性调节、内分泌激素调节、炎症反应、肾素-血管紧张素系统等通路相关。

结论：

急性缺血性中风阴类证、阳类证的lncRNA，miRNA，mRNA表达谱存在差异，阴、阳类证的表型差异可能由血压调节、肾上腺素能受体调节、肾素-血管紧张素系统以及

-氨基丁酸(GABA)等多个通路的共同参与。转录组学特征为研究急性缺血性中风阴类证、阳类证的生物学基础提供了一定的科学依据。

Abstract

Objective:

To obtain the regulatory relationship between genes by screening the differentially expressed long non-coding ribonucleic acid(lncRNA)

microRNA(miRNA) and messenger RNA(mRNA) in serum of patients with Yin and Yang syndromes of acute ischemic stroke

and to discuss the material basis and biological mechanism of formation of Yin and Yang syndromes of acute ischemic stroke from the transcriptome level.

Method:

The microarray chips were adopted to detect expression of lncRNA

mRNA and miRNA in serum of ischemic stroke patients with Yin and Yang syndromes and non-stroke subjects(10 cases each). Differential expression profiles related to Yin and Yang syndromes were selected by conjoint analysis. Further

the obtained differential genes were subjected to antisense lncRNA and mRNA co-expression analysis

gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) functional pathway analysis

and the intergenic regulatory relationship was obtained to predict the target genes of lncRNA. Partial differential genes in 40 patients(10 with Yang syndrome and 30 with Yin syndrome) were verified by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).

Result:

The expression of 227 lncRNA

54 mRNA and 4 miRNA were closely related to Yang syndrome

394 lncRNA and 206 mRNA were closely related to Yin syndrome. Antisense lncRNA RP11-647P12.1 and RP11-677M14.2 may regulate the expression of neuron-derived neurotrophic factor(NDNF) and neurogranin(NRGN) by up-regulating the expression level in Yang syndrome. The differential expression of mRNA between Yin syndrome and Yang syndrome was mainly related to neurotransmitter receptor activity regulation

endocrine hormone regulation

inflammatory response

renin-angiotensin system and other pathways.

Conclusion:

There are differences in the expression profiles of lncRNA

miRNA and mRNA between Yin syndrome and Yang syndrome in acute ischemic stroke

which may be regulated by multiple pathways

such as blood pressure regulation

adrenergic receptor regulation

renin-angiotensin system and

-aminobutyric acid(GABA). The transcriptome characteristics provide scientific basis for studying the biological basis of Yin syndrome and Yang syndrome in acute ischemic stroke.

关键词

Keywords

references

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