黄连素治疗慢性心力衰竭的网络药理学分析  

Network Pharmacological Analysis of Berberine in the Treatment of Chronic Heart Failure

作　　者：张泽宇 闫海峰 闫利 ZHANG Zeyu;YAN Haifeng;YAN Li(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China)

机构地区：[1]天津中医药大学第一附属医院,国家中医针灸临床医学研究中心,天津300381 [2]河南中医药大学第一附属医院,郑州450099 [3]武警特色医学中心烧伤冻伤及组织功能重建研究所,天津300162

出　　处：《中西医结合心脑血管病杂志》2023年第4期617-623,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81903839)。

摘　　要：目的:基于网络药理学和分子对接技术探讨黄连素治疗慢性心力衰竭(CHF)的分子机制。方法:通过GeneCards、STRING等数据库和Cytoscape v3.9.0软件获取CHF核心蛋白;于HERB数据库获取黄连素靶蛋白,并与CHF核心蛋白取交集,利用Cytoscape v3.9.0软件分析黄连素与交集蛋白之间的关系;利用Rx64 4.0.2软件对交集蛋白进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,获得信号通路富集蛋白及筛选核心蛋白;将核心蛋白与黄连素通过AutoDock Vina、PyMOLWin.exe等软件进行分子对接和可视化分析。结果:黄连素可作用于23类CHF核心蛋白,治疗主要涉及调节细胞化学应激反应、DNA结合转录因子活性、炎症反应等功能,白细胞介素-17(IL-17)信号通路、辅助性T细胞17(Th17)分化信号通路、晚期糖基化终末产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路等。通路富集蛋白的核心为转录因子p65(RELA)、c-Jun原癌基因蛋白(JUN)、c-fos原癌基因蛋白(FOS)、丝裂原活化蛋白激酶14(MAPK14)、肿瘤坏死因子(TNF)、白细胞介素-6(IL6),同时可与黄连素强烈结合。结论:黄连素可能主要通过作用于RELA、JUN、FOS、MAPK14、TNF、IL6等蛋白,调节IL-17信号通路、Th17细胞分化信号通路、AGE-RAGE信号通路等,进而在CHF治疗中发挥保护血管内皮、缩小心肌梗死面积和改善心功能等作用。Objective: To explore the molecular mechanism of berberine in the treatment of chronic heart failure(CHF) based on network pharmacology and molecular docking technology.Methods: CHF core protein was obtained by GeneCards, STRING,and Cytoscape v3.9.0 software.The target protein of berberine was obtained from the HERB database, and the intersection with the CHF core protein was obtained.The relationship between berberine and intersection protein were analyzed by Cytoscape v3.9.0 software.Gene Ontology(GO)functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the intersection proteins using Rx64 4.0.2 software to obtain signal pathway enriched proteins and screen core proteins.The core protein and berberine were subjected to molecular docking and visual analysis by AutoDock Vina, PyMOLWin.exe, and other software.Results: Berberine could act on 23 kinds of CHF proteins.Its effect mainly involved cellular response to chemical stress, regulation of DNA-binding transcription factor activity, regulation of inflammatory response, and other biological functions as well as interleukin 17(IL17) signaling pathway, T helper cell 17(Th17) cell differentiation signaling pathway, advanced glycation end product(AGE)-receptor for advanced glycation end products(RAGE) signaling pathway.The core of the enriched proteins in the signaling pathway was transcription factor p65(RELA),c-Jun proto-oncogene(JUN),c-fos proto-oncogene proteins(FOS),mitogen-activated protein kinase 14(MAPK14),tumor necrosis factor(TNF) and interleukin 6(IL6).It could be strongly combined with berberine.Conclusion: Berberine might regulate the IL17 signaling pathway, Th17 cell differentiation signaling pathway, and AGE-RAGE signaling pathway by acting on RELA,JUN,FOS,MAPK14,TNF,IL6,and other proteins.Berberine played its role in the treatment of CHF by protecting the endothelium, reducing the myocardial infarction area, and improving cardiac function.

关 键 词：慢性心力衰竭 黄连素 分子机制 网络药理学 分子对接 

分 类 号：R54[医药卫生—心血管疾病]