首页|网络药理学和分子对接法研究白杨素治疗肺动脉高压的机制

网络药理学和分子对接法研究白杨素治疗肺动脉高压的机制

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目的 基于网络药理学和实验验证研究白杨素防治肺动脉高压(PH)的效果和作用机制.方法 运用PubChem数据库收集白杨素的靶点;采用DisGeNET、GeneCards数据库联合筛选PH的靶点;运用STRING平台构建蛋白-蛋白相互作用网络;使用DAVID和Metescape数据库进行靶点GO功能富集和KEGG通路富集分析;采用AutoDock进行分子对接.构建低氧PH模型,通过考察血流动力学、肺组织肺血管重构及胶原沉积情况来研究白杨素对PH的治疗作用;用蛋白质印迹法验证白杨素对关键靶点蛋白含量表达的影响.结果 表皮生长因子受体(EGFR)、前列腺素内过氧化物合成酶2(PTGS2)、劳斯肉瘤癌基因(SRC)、雌激素受体1(ESR1)、基质金属蛋白酶9(MMP9)是白杨素治疗PH的关键靶点;白杨素与5个关键靶点均能较好地结合.白杨素能明显改善PH大鼠的血流动力学、肺组织肺中小动脉重构及胶原沉积情况,缓解PH引起的SRC、ESR1、EGFR、PTGS2、MMP9蛋白表达量的变化.结论 白杨素治疗PH具有"多靶点-多通路"的特点,可通过与MMP9、EGFR、ESR1等关键靶点结合从而发挥治疗PH的作用.
Study on the therapeutic mechanism of chrysin on pulmonary hypertension by Network pharmacology and molecular docking
OBJECTIVE To study the therapeutic efficacy and underlying mechanism of chrysin in the prevention and treatment of pulmonary hypertension(PH)through a merged approach of Network pharmacology and experimental validation.METHODS The PubChem database was utilized to identify the molecular targets of chrysin,while the DisGeNET and GeneCards databases were employed to select relevant PH targets.The STRING platform was employed to construct a protein-protein interaction network.Functional and pathway enrichment analyses were conducted using the DAVID and Metascape databases for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways,respectively.Molecular docking was conducted using AutoDock software.A hypoxia-induced PH model was established to evaluate the effects of chrysin on PH,focusing on hemodynamics,pulmonary vascular remodeling,and collagen deposition in the lung tissues.Furthermore,the effects of chrysin on key target protein expression were confirmed through Western blot experiments.RESULTS SRC,ESR1,EGFR,PTGS2,and MMP9 were the pivotal targets of chrysin in PH treatment.The preferential binding affinity of chrysin to these critical proteins.Chrysin demonstrated notable efficacy in ameliorating hemodynamic abnormalities,reducing small pulmonary artery remodeling and collagen accumulation in the lungs,and showed modulatory effects on the expression levels of SRC,ESR1,EGFR,PTGS2,and MMP9 in PH conditions.CONCLUSION Our findings indicate that chrysin exerts its therapeutic effects against PH through a"multi-target,multi-pathway"mechanism.Chrysin primarily interacts with key proteins including MMP9,EGFR,and ESR1.

ChrysinHypoxiaPulmonary hypertensionPulmonary artery remodelingCollagen accumulationNetwork pharmacologyMolecular dockingMechanism

楚欣欣、潘思雨、郭绅、陈宇静、祝田田

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新乡医学院药学院河南省心血管重构与药物干预国际联合实验室新乡市心血管重构干预与分子靶向治疗药物研发重点实验室,河南新乡 453003

白杨素 低氧 肺动脉高压 肺血管重构 胶原沉积 网络药理学 分子对接 作用机制

河南省自然科学基金面上项目国家自然科学基金资助项目河南省科技攻关项目

24230042130581800051212102310319

2024

10.13375/j.cnki.wcjps.2024.05.003

华西药学杂志
四川大学,四川省药学会

华西药学杂志

CSTPCD北大核心
影响因子：0.624
ISSN：1006-0103
年,卷(期)：2024.39(5)