生脉救心汤治疗心力衰竭作用机制探讨:基于网络药理学和分子对接技术

Exploration of the Mechanism of Action of Shengmai Jiuxin Decoction in the Treatment of Heart Failure,Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学和分子对接探讨生脉救心汤(SMJXD)治疗心力衰竭的作用机制。方法:通过TCMSP、BATMAN-TCM数据库结合文献收集SMJXD有效成分及靶点,应用GeneCards、OMIM、DisGeNET软件收集心衰疾病靶点,通过Venny 2.1筛选两者的交集靶点,应用Cytoscape 3.10.1对交集靶点进行分析,应用Cytoscape软件构建靶点蛋白互作网络图,通过DAVID数据库进行GO、KEGG富集分析,最后应用AutoDock软件进行分子对接。结果:筛选出SMJXD治疗心力衰竭的12种共有活性成分,其中最关键的是山柰酚、谷甾醇、槲皮素、豆甾醇、β-谷甾醇等;还发现69个核心靶点,其中关键核心靶点是HIF-1α、BCL-2、CASP3、VEGF-α等。分子对接结果显示:HIF-1α与豆甾醇(-7.65 kJ/mol)、CASP3与豆甾醇(-8.04 kJ/mol)、VEGF-α与β-谷甾醇(-9.14 kJ/mol)、BCL-2与豆甾醇(-7.21 kJ/mol)具有最佳结合能。KEGG提示:HIF-1信号通路及其富集的HIF-1α、BCL-2、CASP3、VEGF-α核心靶点疾病相关性最高。GO分析显示:SMJXD影响了基因表达正/负向调控、细胞凋亡正调控等生物途径,还有大分子复合物、细胞外空间等细胞成分,以及酶结合等分子功能。结论:SMJXD可能是在细胞外空间通过酶结合等分子功能形成大分子复合物,干预HIF-1信号通路调控基因表达和细胞凋亡,从而治疗心衰。该结论可为后续深入研究心衰作用机制,开发新的心衰治疗药物开拓新思路。

Objective:To investigate the mechanism of action of Shengmai Jiuxin Decoction(SMJXD)in the treatment of heart failure based on network pharmacology and molecular docking.Methods:TCMSP and BATMAN-TCM databases were used to collect SMJXD active ingredients and targets,GeneCards,OMIM,and DisGeNET software were used to collect heart failure disease targets,Venny 2.1 was used to screen the intersection targets,Cytoscape 3.10.1 was used to analyze the intersection targets,Cytoscape software was used to construct the target protein interaction network diagram,and DAD database was used to perform GO and KEGG enrichment analysis,and finally the molecular docking was performed using AutoDock software.Results:In this study,12 common active components of SMJXD in the treatment of heart failure were screened,among which the most critical ones were kaempferol,sitosterol,quercetin,stigmasterol,β-sitosterol,etc.and 69 core targets,of which the key core targets include HIF-1α,BCL-2,CASP3,VEGF-α,etc.The results showed that HIF-1αhad the best binding energy to stigmasterol(-7.65 kJ/mol),CASP3 to stigmasterol(-8.04 kJ/mol),VEGF-αtoβ-sitosterol(-9.14 kJ/mol),and BCL-2 to stigmasterol(-7.21 kJ/mol).KEGG suggested that the HIF-1 signaling pathway and its enriched core targets of HIF-1α,BCL-2,CASP3 and VEGF-αwere the most disease-related.GO analysis showed that SMJXD affected the positive/negative regulation of gene expression and the positive regulation of apoptosis.Cellular components such as macromolecular complexes,extracellular space,etc.;and molecular functions such as enzyme binding.Conclusion:SMJXD may form macromolecular complexes in the extracellular space through molecular functions such as enzyme binding,interfering with the HIF-1 signaling pathway to regulate gene expression and apoptosis,thereby treating heart failure.This opens up new ideas for the follow-up in-depth study of the mechanism of action of heart failure and the development of new drugs for the treatment of heart failure.