Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease

GUO Junchi; ZHANG Mingyan; ZHAO Yingqiang; LU Meijuan

doi:10.6039/j.issn.1001-0408.2025.17.11

您当前的位置：

首页 >

文章列表页 >

Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease

更新时间：2025-09-29

- Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease
- ZHONGGUO YAOFANG Vol. 36, Issue 17, Pages: 2148-2153(2025)
- 作者机构：
  
  1.天津中医药大学研究生院，天津　301617
  2.天津中医药大学循证医学中心，天津　301617
  3.天津中医药大学第二附属医院心血管内科，天津　300250
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.17.11
  CLC： R972;R541.4
- Received：17 March 2025，
  
  Revised：2025-08-11，
  
  Accepted：11 August 2025，
  
  Published：15 September 2025
- 稿件说明：
移动端阅览
郭俊池,张明妍,赵英强,等.通脉养心丸治疗冠心病的核心基因及其潜在免疫和代谢机制[J].中国药房,2025,36(17):2148-2153.

GUO Junchi,ZHANG Mingyan,ZHAO Yingqiang,et al.Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease[J].ZHONGGUO YAOFANG,2025,36(17):2148-2153.
郭俊池,张明妍,赵英强,等.通脉养心丸治疗冠心病的核心基因及其潜在免疫和代谢机制[J].中国药房,2025,36(17):2148-2153. DOI： 10.6039/j.issn.1001-0408.2025.17.11.

GUO Junchi,ZHANG Mingyan,ZHAO Yingqiang,et al.Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease[J].ZHONGGUO YAOFANG,2025,36(17):2148-2153. DOI： 10.6039/j.issn.1001-0408.2025.17.11.

摘要

目的

揭示与通脉养心丸治疗冠心病相关的核心基因并预测其潜在的免疫及代谢机制。

方法

使用UK Biobank 蛋白质数量性状位点（pQTL）、冰岛pQTL数据和全基因组关联研究数据进行孟德尔随机化（MR）分析，筛选出与通脉养心丸治疗冠心病相关的核心基因，并通过转录组测序数据验证其表达量变化情况；进一步进行免疫细胞与血浆代谢物的中介效应分析，探索核心基因的下游调控网络。

结果

共有62个阳性pQTL基因与冠心病存在显著因果关联，经MR分析和转录组测序数据验证，发现

FAM3D

、

OXT

和

ENPP5

为通脉养心丸治疗冠心病的核心基因。转录组测序结果显示，经通脉养心丸治疗后，

FAM3D

、

OXT

的表达水平显著降低（

＜0.01），

ENPP5

的表达水平显著升高（

＜0.05）。免疫细胞与血浆代谢物中介效应分析结果表明，

FAM3D

、

OXT

和

ENPP5

可通过调节调节性T细胞、表达CD11c和CD62L的髓系树突状细胞等免疫途径或调控脂质和脂肪酸代谢途径、胆固醇和胆汁酸代谢途径等来实现对冠心病的正/负向调节。

结论

本研究确定了

FAM3D

、

OXT

和

ENPP5

是通脉养心丸治疗冠心病的核心基因，并证明了其可能通过调节免疫细胞及血浆脂肪酸、胆汁酸等代谢途径发挥作用。

Abstract

OBJECTIVE

To identify core genes associated with the treatment of coronary heart disease （CHD） with Tongmai yangxin pills， and predict their potential immunological and metabolic mechanisms.

METHODS

Mendelian randomization （MR） analysis was conducted using protein quantitative trait loci （pQTL） data from the UK Biobank and Icelandic，and data from genome-wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes.

RESULTS

A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes

FAM3D

，

OXT

， and

ENPP5

-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills， the expression levels of

FAM3D

and

OXT

were significantly reduced （

＜0.01）， while the expression level of

ENPP5

was significantly increased （

＜0.05）. Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively r

egulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L， as well as through metabolic pathways related to lipid and fatty acid metabolism， cholesterol metabolism， and bile acid metabolism.

CONCLUSIONS

This study identified

FAM3D

，

OXT

， and

ENPP5

as core genes associated with the treatment of CHD by Tongmai yangxin pills， which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.

关键词

Keywords

references

HEIANZA Y ， WANG X ， KOU M H ， et al . Circulating dimethylguanidino valeric acid，dietary factors，and risk of coronary heart disease [J ] . Cardiovasc Res ， 2024 ， 120 （ 16 ）： 2147 - 2154 .

MCEVOY J W ， JENNINGS C ， KOTSEVA K ， et al . Variation in secondary prevention of coronary heart disease：the INTERASPIRE study [J ] . Eur Heart J ， 2024 ， 45 （ 39 ）： 4184 - 4196 .

ARNOLD N ， BLAUM C ， GOßLING A ， et al . C-reactive protein modifies lipoprotein（a）-related risk for coronary heart disease：the BiomarCaRE project [J ] . Eur Heart J ， 2024 ， 45 （ 12 ）： 1043 - 1054 .

NORLAND K ， SCHAID D J ， NADERIAN M ， et al . Associations of self-reported race，social determinants of health，and polygenic risk with coronary heart disease [J ] . J Am Coll Cardiol ， 2024 ， 84 （ 22 ）： 2157 - 2166 .

王显，安冬青，中华中医药学会介入心脏病学分会代表编制组 . 通脉养心丸治疗冠心病心绞痛（气阴两虚证）临床应用专家共识 [J ] . 中华中医药学刊， 2021 ， 39 （ 9 ）： 253 - 258 .

FAN Y Y ， MAN S L ， LI H F ， et al . Analysis of bioactive components and pharmacokinetic study of herb-herb interactions in the traditional Chinese patent medicine Tongmai yangxin pill [J ] . J Pharm Biomed Anal ， 2016 ， 120 ： 364 - 373 .

JONES T ， FENG J J ， LUYTIES O ， et al . TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network [J ] . Sci Adv ， 2025 ， 11 （ 9 ）： eadr9660 .

YANG Q Q ， YANG Q ， WU X Y ， et al . Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure [J ] . Cell Rep Med ， 2024 ， 5 （ 2 ）： 101382 .

MA Z ， FREY N ， RANGREZ A Y . Blood plasma metabolites and heart failure risk：insights from Mendelian randomization analysis [J ] . Eur Heart J ， 2024 ， 45 （ Suppl.1 ）：ehae666.1205.

FERKINGSTAD E ， SULEM P ， ATLASON B A ， et al . Large-scale integration of the plasma proteome with gene- tics and disease [J ] . Nat Genet ， 2021 ， 53 （ 12 ）： 1712 - 1721 .

CHEN J X ， LI Y ， ZHANG Y B ， et al . Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease：an observational and Mendelian randomization analysis [J ] . Metabolism ， 2024 ， 154 ： 155817 .

YE C J ， LIU D ， CHEN M L ， et al . Mendelian randomization evidence for the causal effect of mental well-being on healthy aging [J ] . Nat Hum Behav ， 2024 ， 8 （ 9 ）： 1798 - 1809 .

LIAO J ， BEI L Y ， NIE P B ， et al . DNA methylation-regulated ZDHHC13 promotes the progression of Parkinson’s disease [J ] . Mol Neurobiol ， 2025 ， 62 （ 7 ）： 9162 - 9169 .

ABRAMOWITZ S A ， BOULIER K ， KEAT K ， et al . Evaluating performance and agreement of coronary heart disease polygenic risk scores [J ] . JAMA ， 2025 ， 333 （ 1 ）： 60 - 70 .

CHEN R ， CHEN T ， WANG T Q ， et al . Tongmai yangxin pill reduces myocardial No-reflow via endothelium-dependent NO-cGMP signaling by activation of the cAMP/PKA pathway [J ] . J Ethnopharmacol ， 2021 ， 267 ： 113462 .

SHEN Y C ， DONG Z G ， FAN F F ， et al . Targeting cytokine-like protein FAM3D lowers blood pressure in hypertension [J ] . Cell Rep Med ， 2023 ， 4 （ 6 ）： 101072 .

MOSER C ， GOSSELÉ K A ， BALAZ M ， et al . FAM3D：a gut secreted protein and its potential in the regulation of glucose metabolism [J ] . Peptides ， 2023 ， 167 ： 171047 .

LV J L ， PAN C ， CAI Y P ， et al . Plasma metabolomics reveals the shared and distinct metabolic disturbances associated with cardiovascular events in coronary artery disease [J ] . Nat Commun ， 2024 ， 15 ： 5729 .

HAAS B W ， FILKOWSKI M M ， COCHRAN R N ， et al . Epigenetic modification of OXT and human sociability [J ] . Proc Natl Acad Sci USA ， 2016 ， 113 （ 27 ）： E3816 - E3823 .

TAKAYA K ， KISHI K . Regulation of ENPP5，a senescence-associated secretory phenotype factor，prevents skin aging [J ] . Biogerontology ， 2024 ， 25 （ 3 ）： 529 - 542 .

LIN Z T ， PAN W . A robust cis-Mendelian randomization method with application to drug target discovery [J ] . Nat Commun ， 2024 ， 15 ： 6072 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Metabolite identification and metabolic pathway analysis of pirtobrutinib in rats

Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis

Research progress on metabonomics of traditional Chinese medicine in the treatment of ulcerative colitis

UPLC-MS/MS法鉴定五味子酯甲在大鼠体内的代谢产物

Related Author

DONG Ruihua

WU Jingxuan

LI Jiangshuo

HOU Mengyu

YIN Hang

LI Jie

ZHANG Meijuan

XIANG Shijian

Related Institution

Dept. of Research Ward， Beijing Friendship Hospital， Capital Medical University

School of Chinese Materia Medica， Beijing University of Chinese Medicine

School of Pharmacy， Guangdong Medical University

Dept. of Pharmacy， the Seventh Affiliated Hospital of Sun Yat-sen University

Blood Purification Center of Huidong County People’s Hospital

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰