中国中医药信息杂志2025，Vol.32Issue(10)：41-50,10.DOI:10.19879/j.cnki.1005-5304.202505063
基于miR-126/PI3K/Akt轴探讨温阳益气活血方治疗慢性心力衰竭作用机制
Exploration on the Mechanism of Wenyang Yiqi Huoxue Prescription in the Treatment of Chronic Heart Failure Based on miR-126/PI3K/Akt Axis
摘要
Abstract
Objective To explore the mechanism of Wenyang Yiqi Huoxue Prescription(WYYQHXP)in the treatment of chronic heart failure(CHF)by regulating miR-126-3p and PI3K/Akt signaling pathway based on network pharmacology and experimental studies.Methods Active components and targets of WYYQHXP were obtained through TCMSP,SwissTargetPrediction,SwissADME and PubChem.Four miRNA databases were used to obtain miR-126-3p targets,and four disease databases were used to obtain CHF related targets.The intersection of the three was taken as the potential target of action;the protein-protein interaction network relationships of potential targets were explored using STRING and Cytoscape 3.9.1 software,and the main active components and core targets were screened;GO and KEGG pathway enrichment analysis was performed using R 4.2.1 software;Molecular docking was performed on the main active components with the core targets.Isoproterenol was used to induce a rat model of CHF with qi deficiency and blood stasis syndrome,and intervened with WYYQHXP.MiR-126-3p and core target expression in coronary endothelial cells were detected by immunohistochemistry,RT-qPCR,and Western blot.Results Network pharmacology screened main active components of WYYQHXP,including β-sitosterol,doustanol,kaempferol,quercetin,baicalein and luteolin,and the core targets of EGFR,VEGFA and AKT1;KEGG was enriched to the signaling pathways such as PI3K/Akt,and the 3 core targets were distributed to the PI3K/Akt signaling pathway;molecular docking showed good binding ability of β-sitosterol and stigmasterol to three core targets.Animal experiments showed that WYYQHXP could increase left ventricular ejection fraction and left ventricular fractional shortening in model rats(P<0.01),reduce serum brain natriuretic peptide content(P<0.01),increase expression of miR-126-3p(P<0.05,P<0.01,P<0.001),the medium-dosage of WYYQHXP could increase mRNA and protein expressions of EGFR,PI3K,AKT1 and VEGFA in coronary endothelial cells(P<0.01).Conclusion WYYQHXP may activate PI3K/Akt signaling pathway by acting on miR-126-3p,thereby restoring endothelial dependent vasodilation of coronary arteries,repairing endothelial dysfunction of coronary arteries,and treating CHF.关键词
网络药理学/慢性心力衰竭/miR-126-3p/PI3K/Akt信号通路/温阳益气活血方Key words
network pharmacology/chronic heart failure/miR-126-3p/PI3K/Akt signaling pathway/Wenyang Yiqi Huoxue Prescription分类
医药卫生引用本文复制引用
张贤儒,祁青明,祁永福,杜珂,马晓贞,刘畅..基于miR-126/PI3K/Akt轴探讨温阳益气活血方治疗慢性心力衰竭作用机制[J].中国中医药信息杂志,2025,32(10):41-50,10.基金项目
青海省中藏医药管理局科研课题项目(J2023006) （J2023006）
中央转移支付财政支持项目-中药创新能力提升项目(2023年) （2023年）
