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景鹤养心舒治疗慢性心力衰竭的作用机制

Mechanism of Jinghe yangxinshu in the Treatment of Chronic Heart Failure based on Network Pharmacology and Molecular docking

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【作者】 胡华鹏朱金燕李杰平赵星刘明

【Author】 HU Huapeng;ZHU Jinyan;LI Jieping;ZHAO Xing;LIU Ming;Yunnan University of Chinese Medicine;Zhaotong Health Vocational College;Kunming Hospital of Traditional Chinese Medicine;

【通讯作者】 刘明;

【机构】 云南中医药大学昭通卫生职业学院昆明市中医医院

【摘要】 目的:通过网络药理学和分子对接研讨景鹤养心舒治疗慢性心力衰竭的作用机制。方法:利用TCMSP数据库、TCMID数据库及SwissTargetPrediction数据库收集景鹤养心舒的化学成分及对应蛋白靶点,再以Uniprot数据库将蛋白靶点转化为基因靶点。通过GeneCards数据库、DisGeNET数据库获取慢性心力衰竭疾病基因靶点。将药物靶点和疾病靶点输入Venny图中分析得到交集靶点。在Cytoscape 3.9.1软件构建“药物-成分-靶点-疾病”网络模型,筛选出关键化合物和核心靶点;应用STRING数据库构建蛋白互作网络图;以DAVID数据库进行GO富集分析和KEGG通路富集分析。最后通过分子对接对核心成分与关键靶点之间的活性进行验证。结果:筛选出景鹤养心舒中182种有效成分及499个相关靶点,慢性心力衰竭的疾病靶点199个,通过韦恩图获得共同靶点42个。分析得到槲皮苷、山奈酚、木犀草素、β-谷甾醇、异鼠李素是景鹤养心舒治疗慢性心力衰竭的重要化学物质,IL6、TNF、NOS3、VEGFA、ACE是景鹤养心舒作用于慢性心力衰竭的关键靶点。GO分析结果显示,景鹤养心舒治疗慢性心力衰竭的生物学过程主要涉及炎症反应、缺氧反应、细胞增殖调亡的调控等方面;KEGG富集通路包括流体剪切应力与动脉粥样硬化通路、AGE-RAGE信号通路等。分子对接结果显示核心成分与关键靶点之间对接良好。结论:景鹤养心舒通过多成分、多靶点、多通路以抑制心脏重塑、延缓心肌细胞凋亡、调节氧化应激、影响炎性因子、改善心脏收缩舒张功能、减轻心脏后负荷等,从而发挥治疗慢性心力衰竭的作用。

【Abstract】 Objective: To study the mechanism of Jinghe Yangxinshu in the treatment of chronic heart failure through network pharmacology and molecular docking. Methods: TCMSP database, TCMID database and SwissTargetPrediction database were used to collect the chemical components and corresponding protein targets of Jinghe Yangxinshu, and then the protein targets were converted into gene targets by Uniprot database. Obtain gene targets of chronic heart failure disease through GeneCards database and DisGeNET database. Enter the drug target and disease target into the Venny graph to analyze the intersection target. “Drug-Component-Target-Disease” network model was building in Cytoscape 3.9.1 software, and screen out key compounds and core targets; use the STRING database to construct a protein interaction network diagram; use the DAVID database for GO enrichment analysis and KEGG pathways Enrichment analysis. Finally, the activity between the core components and key targets was verified by molecular docking. Results: 182 active ingredients and 499 related targets in Jinghe Yangxinshu were screened out, 199 disease targets for chronic heart failure, and 42 common targets were obtained through the Venn diagram. The analysis shows that quercitrin, kaempferol, luteolin, β-sitosterol and isorhamnetin are the important chemical substances of Jinghe Yangxinshu in treating chronic heart failure. IL6, TNF, NOS3, VEGFA and ACE are the important chemical substances of Jinghe Yangxinshu. A key target of diastolic action in chronic heart failure. The results of GO analysis showed that the biological process of Jinghe Yangxinshu in the treatment of chronic heart failure mainly involves the regulation of inflammatory response, hypoxic response, cell proliferation and apoptosis; KEGG enriched pathways include fluid shear stress and atherosclerosis pathway, AGE-RAGE signaling pathway, etc. Molecular docking results showed that the core components were well docked with key targets. Conclusion: Jinghe Yangxinshu inhibits cardiac remodeling, delays cardiomyocyte apoptosis, regulates oxidative stress, affects inflammatory factors, improves cardiac systolic and diastolic function, and reduces cardiac afterload through multiple components, multiple targets, and multiple pathways., so as to play a role in the treatment of chronic heart failure.

【基金】 云南省“万人计划”名医专项人才项目(云卫人发[2019]35号)
  • 【文献出处】 中医药临床杂志 ,Clinical Journal of Traditional Chinese Medicine , 编辑部邮箱 ,2023年02期
  • 【分类号】R285
  • 【下载频次】20
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