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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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| 篇名： | 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 |
| TITLE： | Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease |
| 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UKBiobank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。 |
| 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， 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. |
| 期刊： | 2025年第36卷第17期 |
| 作者： | 郭俊池；张明妍；赵英强；路美娟 |
| AUTHORS： | GUO Junchi，ZHANG Mingyan，ZHAO Yingqiang，LU Meijuan |
| 关键字： | 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 |
| KEYWORDS： | Tongmai yangxin pills； Mendelian randomization； coronary heart disease； protein quantitative trait loci； core |
| 阅读数： | 3 次 |
| 本月下载数： | 0 次 |
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