摘要
目的:探讨稳心汤对急性心肌梗死后心力衰竭(AMI-HF)气虚血瘀证患者心功能的影响及其作用机制。方法:60例AMI-HF气虚血瘀证患者随机分为治疗组和对照组,两组均予基础西药治疗,治疗组在此基础上加用稳心汤口服治疗,疗程4周。观察两组治疗前后的N末端脑钠肽前体(NT-proBNP)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)与中医证候积分水平。治疗组与对照组分别随机抽取7例患者进行外周血单个核细胞转录组测序,利用DESeq2软件以|log_(2)差异倍数|≥2且P<0.01筛选差异表达基因(DEGs)。对DEGs进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析,使用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络并筛选关键靶点。结果:与对照组比较,治疗组治疗后NT-proBNP、LVEDD及中医证候积分明显降低、LVEF明显升高(P<0.05)。共筛选出DEGs 270个,其中上调基因89个,下调基因181个。GO富集分析表明,DEGs主要涉及细胞过程、代谢过程、生物调节、细胞结构、蛋白活性、调节因子活性等功能;KEGG通路分析显示,DEGs主要通过参与三羧酸循环、氧化磷酸化、丙酮酸代谢、线粒体自噬、Apelin信号通路、对叉头框蛋白O(FoxO)信号通路等发挥生物学作用。PPI分析共筛选出节点蛋白136个,相互作用关系425条边;筛选出10位关键靶点,分别为丝裂原活化蛋白激酶13(MAPK13)、非受体型酪氨酸蛋白激酶(LYN)、趋化因子C-X-C-基序受体4(CXCR4)、丝状伪足相关基因(RHOF)、Janus激酶3(JAK3)、多配体蛋白聚糖-1(SDC1)、C-X-C基序趋化因子11(CXCL11)、多巴胺D2受体(DRD2)、蛋白激酶Cβ(PRKCB)、磷脂酰肌醇4-磷酸3-激酶催化亚基2β(PIK3C2B)。结论:稳心汤可有效改善AMI-HF气虚血瘀证患者的心功能,其作用机制可能与细胞信号传导、功能调节与能量代谢、细胞免疫及炎症反应有关,有望为稳心汤的临床应用提供新思路及证据支撑。
Objective:To investigate the effect and mechanism of Wenxin decoction on cardiac function in patients with acute myocardial infarction-induced heart failure(AMI-HF)of Qi deficiency and blood stasis syndrome.Methods:A total of 60 patients with AMI-HF of Qi deficiency and blood stasis syndrome were randomly divided into a treatment group and a control group.Both groups received standard Western medical therapy,while the treatment group additionally received Wenxin Decoction orally for 4 weeks.The levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),and traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed in both groups.Peripheral blood mononuclear cells from seven randomly selected patients in each group were subjected to transcriptome sequencing.Differentially expressed genes(DEGs)were screened using DESeq2 software with|log2(fold change)|≥2 and P<0.01.Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed on the DEGs.The STRING database and Cytoscape software were used to construct a protein-protein interaction(PPI)network and identify key targets.Results:Compared with the control group,the treatment group showed significantly decreased NT-proBNP,LVEDD,and TCM syndrome scores,and significantly increased LVEF after treatment(P<0.05).A total of 270 DEGs were identified,including 89 upregulated genes and 181 downregulated genes.GO enrichment analysis showed that the DEGs were mainly involved in functions such as cellular processes,metabolic processes,biological regulation,cellular structure,protein activity,and regulator activity.KEGG pathway analysis indicated that the DEGs primarily exerted biological effects through participation in the tricarboxylic acid(TCA)cycle,oxidative phosphorylation,pyruvate metabolism,mitophagy,the Apelin signaling pathway,and the FoxO signaling pathway.PPI network analysis identified 136 node proteins and 425 interaction edges.The top 10 key targets were mitogen-activated protein kinase 13(MAPK13),non-receptor tyrosine-protein kinase(LYN),C-X-C motif chemokine receptor 4(CXCR4),Ras homolog family member F(RHOF),Janus kinase 3(JAK3),syndecan-1(SDC1),C-X-C motif chemokine ligand 11(CXCL11),dopamine receptor D2(DRD2),protein kinase C beta(PRKCB),and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta(PIK3C2B).Conclusion:Wenxin decoction can effectively improve cardiac function in AMI-HF patients with Qi deficiency and blood stasis syndrome.Its mechanism may be related to the regulation of cell signal transduction,functional modulation,energy metabolism,cellular immunity,and inflammatory response,providing new insights and supporting evidence for the clinical application of Wenxin Decoction.
作者
陶诗怡
李军
薛甜甜
于林童
黄炫淳
解紫从
苏丽澜
孟超
TAO Shiyi;LI Jun;XUE Tiantian;YU Lintong;HUANG Xuanchun;XIE Zicong;SU Lilan;MENG Chao(Beijing University of Chinese Medicine,Beijing 100029,China;Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第23期130-137,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
中央高水平中医医院临床科研业务费专项(HLCMHPP2023065)
国家自然科学基金面上项目(82474494)
国家重点研发计划项目(2022YFC3500102)
首都卫生发展科研专项重点攻关项目(2020-1-4151)。
关键词
稳心汤
急性心肌梗死
心力衰竭
气虚血瘀证
转录组学
网络药理学
Wenxin decoction
acute myocardial infarction
heart failure
Qi deficiency and blood stasis syndrome
transcriptomics
network pharmacology
