| 74 | 0 | 26 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 采用网络药理学和分子对接的方法探讨川芎嗪治疗缺氧性肺动脉高压的分子机制。方法 利用SwissTargetPrediction、BATMAN-TCM和PharmMapper数据库获得川芎嗪作用靶点；检索GeneCards数据库获得缺氧性肺动脉高压(hypoxic pulmonary hypertension, HPH)疾病靶点，将药物靶点和疾病靶点取交集后获得川芎嗪治疗缺氧性肺动脉高压的潜在作用靶点。接着，利用R软件进行基因本体(gene ontology, GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析及可视化。通过STRING数据库构建蛋白-蛋白相互作用(protein-protein interaction, PPI)网络，并使用Cytoscape软件构建网络以及筛选核心靶点。最后，利用AutoDockTools进行分子对接来验证网络分析结果。结果 共识别出川芎嗪治疗缺氧性肺动脉高压的潜在作用靶点59个。富集分析结果揭示了川芎嗪治疗缺氧性肺动脉高压主要涉及激素调节、细胞增殖、炎性反应等功能及通路。在分析PPI网络后发现排名前10的核心靶点为EGFR、ESR1、PPARG、CASP3、HSP90AA1、GSK3B、CYP3A4、MMP2、AR和PTPN11。分子对接结果表明，核心靶点与化合物结合良好，尤其是GSK3B、MMP2和AR。结论 川芎嗪可能通过影响核心靶点调控多种信号通路来参与缺氧性肺动脉高压的过程。GSK3B、MMP2和AR可能是值得进一步研究的核心靶点。本研究为川芎嗪治疗缺氧性肺动脉高压的药理学研究提供了研究基础和依据。
Abstract：Objective To elucidate the potential molecular mechanisms underlying the effects of Ligustrazine on hypoxic pulmonary hypertension(HPH) using network pharmacology and molecular docking.Methods Potential targets of Ligustrazine were identified using the SwissTargetPrediction, BATMAN-TCM, and PharmMapper databases, whereas HPH-related targets were retrieved from the GeneCards database. The overlapping drug-and disease-related targets were identified as potential therapeutic targets of Ligustrazine for HPH. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were subsequently performed and visualized using R software. A protein–protein interaction(PPI) network was constructed using the STRING database, and Cytoscape software was used for network analysis and core target identification. Finally, molecular docking was performed using AutoDockTools to evaluate the binding of Ligustrazine to the identified core targets.Results A total of 59 potential therapeutic targets of Ligustrazine for HPH were identified. Enrichment analyses indicated that these targets were primarily associated with biological functions and signaling pathways related to hormone regulation, cell proliferation, and inflammatory responses. PPI network analysis identified EGFR, ESR1, PPARG, CASP3, HSP90AA1, GSK3B, CYP3A4, MMP2, AR, and PTPN11 as the top 10 core targets. Molecular docking demonstrated favorable binding of Ligustrazine to the core targets, with particularly strong binding to GSK3B, MMP2, and AR.Conclusion Ligustrazine may exert therapeutic effects against HPH by modulating multiple signaling pathways through key molecular targets. GSK3B, MMP2, and AR may represent important core targets warranting further investigation. These findings provide a theoretical basis for further pharmacological and experimental studies of Ligustrazine in the treatment of HPH.
[1] Chen Y,Lu W,Yang K,et al.Tetramethylpyrazine:A promising drug for the treatment of pulmonary hypertension[J].British Journal of Pharmacology,2020,177(12):2743-2764.
[2] Zhang X,Chen J,Xu P,et al.Protective effects of astragaloside IV against hypoxic pulmonary hypertension[J].MedChemComm,2018,9(10):1715-1721.
[3] Yu X,Wu M,Meng Q,et al.Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells[J].Clinical and Translational Science,2023,16(8):1369-1380.
[4] Cai Y N,Barer G R.Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats[J].Clinical Science,1989,77(5):515-520.
[5] Nie X,Wu Z,Shang J,et al.Curcumol suppresses endothelial-to-mesenchymal transition via inhibiting the AKT/GSK3β signaling pathway and alleviates pulmonary arterial hypertension in rats[J].European Journal of Pharmacology,2023,943:175546.
[6] Tian X,Zhang X,Feng Y,et al.Correction to:astragaloside IV in hypoxic pulmonary hypertension:in vivo and in vitro experiments[J].Applied Biochemistry and Biotechnology,2023,195(2):1604.
[7] Xin N,Zhang X,Feng Y,et al.Astragaloside IV in hypoxic pulmonary hypertension:an in vivo and in vitro experiments[J].Applied Biochemistry and Biotechnology,2022,194(12):6319-6334.
[8] Li C,Zhu H,Zhang S,et al.Astragaloside IV ameliorates pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension by restraining the T follicular helper cell response and expanding T follicular regulatory cell response[J].Phytomedicine:International Journal of Phytotherapy and Phytopharmacology,2022,102:154171.
[9] Li L,Zhang D,Yao W,et al.Ligustrazine exerts neuroprotective effects via circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury[J].Brain Research Bulletin,2022,190:244-255.
[10] Zhang C,Guan D,Jiang M,et al.Efficacy of leflunomide combined with ligustrazine in the treatment of rheumatoid arthritis:prediction with network pharmacology and validation in a clinical trial[J].Chinese Medicine,2019,14:26.
[11] Ye T,Li Y,Xiong D,et al.Combination of danshen and ligustrazine has dual anti-inflammatory effect on macrophages and endothelial cells[J].Journal of Ethnopharmacology,2021,266:113425.
[12] Nakanishi H,Morikawa S,Kitahara S,et al.Morphological characterization of pulmonary microvascular disease in bronchopulmonary dysplasia caused by hyperoxia in newborn mice[J].Medical Molecular Morphology,2018,51(3):166-175.
[13] Morris H,Denver N,Gaw R,et al.Sex differences in pulmonary hypertension[J].Clinics in Chest Medicine,2021,42(1):217-228.
[14] Gonçalves A E de S S,Rocha G Z,Marin R,et al.Pulmonary hypertension in obese mice is accompanied by a reduction in PPAR-γ expression in pulmonary artery[J].Frontiers in endocrinology,2021,12:701994.
[15] Xiao S,Yang Z,Lv R,et al.miR-135b contributes to the radioresistance by targeting GSK3β in human glioblastoma multiforme cells[J].PLOS One,2014,9(9):e108810.
[16] Zhang W,Li Y,Xi X,et al.MicroRNA-15a-5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP-2 signaling pathway[J].International Journal of Molecular Medicine,2020,45(2):461-474.
基本信息:
中图分类号:R285
引用信息:
[1]谢浩,邓明彬,杨齐.基于网络药理学和分子对接探讨川芎嗪治疗缺氧性肺动脉高压的作用机制[J].微量元素与健康研究,2026,43(05):1-7.
基金信息:
泸州市人民政府与西南医科大学科技战略合作计划(2024LZXNYDJ028,2024LZXNYDJ004); 西南医科大学心血管医学研究所项目(2022YFS0607-B4)
2026-09-30
2026-09-30