血管性认知障碍肾阳虚证的调查研究及DNA甲基化本质  

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

作　　者：刘晓林 丁小燕 刘藜 王红芹 祁轶斐 童文新[1] 陈宝鑫[2] 周庆兵[1] 张颖[1] LIU Xiaolin;DING Xiaoyan;LIU Li;WANG Hongqin;QI Yifei;TONG Wenxin;CHEN Baoxin;ZHOU Qingbing;ZHANG Ying(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[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

出　　处：《中国实验方剂学杂志》2023年第6期111-119,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2018YFC1704303);中国中医科学院科技创新工程项目(C12021A01407)。

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1902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。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 1902 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 Yan

关 键 词：血管性认知障碍 肾阳虚证 DNA甲基化 病证结合 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24