Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence

LIU Xiaolin; DING Xiaoyan; LIU Li; WANG Hongqin; QI Yifei; TONG Wenxin; CHEN Baoxin; ZHOU Qingbing; ZHANG Ying

doi:10.13422/j.cnki.syfjx.20230216

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Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence

更新时间：2023-02-15

- Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 6, Pages: 111-119(2023)
- 作者机构：
  
  1.中国中医科学院西苑医院，北京 100091
  2.北京中医药大学东方医院，北京 100078
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230216
  CLC： R284.2;R285;R289;R287;R22;R2-031;R33;R24
- Published：20 March 2023，
  
  Published Online：14 January 2023，
  
  Received：07 November 2022，
- 稿件说明：
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刘晓林,丁小燕,刘藜等.血管性认知障碍肾阳虚证的调查研究及DNA甲基化本质[J].中国实验方剂学杂志,2023,29(06):111-119.

LIU Xiaolin,DING Xiaoyan,LIU Li,et al.Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):111-119.
刘晓林,丁小燕,刘藜等.血管性认知障碍肾阳虚证的调查研究及DNA甲基化本质[J].中国实验方剂学杂志,2023,29(06):111-119. DOI： 10.13422/j.cnki.syfjx.20230216.

LIU Xiaolin,DING Xiaoyan,LIU Li,et al.Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):111-119. DOI： 10.13422/j.cnki.syfjx.20230216.

摘要

目的

在病证结合背景模式下，调查血管性认知障碍肾阳虚证的分布情况并从DNA甲基化角度探讨血管性认知障碍肾阳虚证的生物学内涵，为未来中医药治疗该病证提供表观遗传学层面的靶点。

方法

2020年9月至2022年11月，通过量表对北京社区居民进行认知障碍筛查，对血管性认知障碍（VCI）患者进行证候分析；后纳入VCI肾阳虚证患者与健康对照者，采集外周血，采用Illumina Human Methylation 850K BeadChip对受试者的外周静脉血进行全基因组DNA甲基化检测，筛选差异甲基化基因并对其进行生信分析。

结果

研究共调查1 902人，患有VCI的人数为201例，占总调查人数的10.57%，其中肾阳虚证者占72.14%；甲基化结果显示，与正常组比较，VCI组有386个差异甲基化位点，可注释到136个基因。京都基因与基因组百科全书（KEGG）信号通路富集分析显示，两组间差异基因主要涉及哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、雌激素（Estrogen）信号通路、环磷酸腺苷（cAMP）信号通路等通路。蛋白质-蛋白质相互作用（PPI）网络分析显示，表皮生长因子受体（EGFR）、EGF、信号转导和转录激活因子3（STAT3）等甲基化差异基因在网络中占有重要地位。

结论

VCI以肾阳虚证为主要证型，甲基化差异基因EGFR、EGF、STAT3等及相关差异通路mTOR信号通路、Estrogen信号通路、cAMP信号通路可能在认知障碍肾阳虚证的发生发展中占有重要作用。

Abstract

Objective

To investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future.

Method

Community residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis.

Result

A total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network.

Conclusion

Kidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

关键词

血管性认知障碍肾阳虚证DNA甲基化病证结合

Keywords

vascular cognitive impairmentkidney Yang deficiency syndromeDNA methylationcombination of disease and syndrome

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