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·药物与临床·
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
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郭俊池 ，张明妍 ，赵英强 ，路美娟 （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
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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）
中图分类号 R972；R541.4 文献标志码 A 文章编号 1001-0408（2025）17-2148-06
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（P＜0.01），ENPP5的表达水平显著升高（P＜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。
关键词 通脉养心丸；孟德尔随机化；冠心病；蛋白质数量性状位点；核心基因；免疫细胞；代谢途径
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（1. School of Graduate， Tianjin University of
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Traditional Chinese Medicine， Tianjin 301617， China；2. Evidence-based Medicine Center， Tianjin University of
Traditional Chinese Medicine， Tianjin 301617， China；3. Dept. of Cardiology， the Second Affiliated Hospital of
Tianjin University of Traditional Chinese Medicine， Tianjin 300250， China）
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 （P＜0.01）， while the expression level of ENPP5 was significantly increased （P＜0.05）. Mediation analyses
between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate 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，
Δ 基金项目 国家自然科学基金面上项目（No.82374619）；天津市 cholesterol metabolism， and bile acid metabolism.
卫生健康委员会中医中西医结合科研课题（No.2023027） CONCLUSIONS This study identified FAM3D，OXT， and
＊第一作者 硕士研究生。研究方向：中医药防治心血管疾病的临
ENPP5 as core genes associated with the treatment of CHD by
床与基础研究。E-mail：Guo_Junchi20010723@163.com
# 通信作者 副主任医师，硕士生导师。研究方向：中医药防治心 Tongmai yangxin pills， which may exert therapeutic effects via
血管疾病的临床与基础研究。E-mail：lmj830127@163.com modulation of immune cells and plasma metabolic pathways
· 2148 · China Pharmacy 2025 Vol. 36 No. 17 中国药房 2025年第36卷第17期
