附子对阿霉素诱导心肌损伤保护的潜在机制  

Potential Mechanism of Protection of Fuzi Against Adriamycin-induced Myocardial Injury

作　　者：陈星羽 贺巧 饶琴 雷谊宁 李彩蓉[1] 张朝阳 CHEN Xing-yu;HE Qiao;ZHANG Cao-yang(School of Clinical Medicine,Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部临床医学院,湖北咸宁437100 [2]咸安区中医医院

出　　处：《湖北科技学院学报（医学版）》2024年第6期482-487,共6页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：湖北科技学院大学生创新创业训练计划项目(S202210827033)。

摘　　要：目的通过网络药理学和细胞实验探究附子对阿霉素诱导的心肌损伤的潜在机制。方法通过TCMSP、SWISS、Chemal和Super-ped数据库对阿霉素和附子进行活性化合物的鉴定及靶点的预测,通过Genecard数据库对心肌损伤的靶点进行预测;利用Cytoscape 3.8.0软件构建“成分-靶点”网络关系图;以STRING数据库构建PPI网络图,并通过DAVID数据库进行GO分析和KEGG分析;利用分子对接和分子动力学验证核心靶点与活性化合物的结合能力;最后通过细胞实验进行初步验证。结果2,7-二去乙酰基-2,7-二苯酰一云南紫杉宁F(2,7-Dideacetyl-2,7-dibenzoyl-taxayunnanine F)、多根乌头碱(karakoline)、异塔拉萨定(isotalatizidine)可能是附子对阿霉素诱导的心肌损伤的潜在活性化合物,其中MAPK1、MAPK3和MC4R可能是附子对阿霉素诱导的心肌损伤的潜在靶点,神经活动配体与受体的相互作用(Neuroactive ligand-receptor interaction)信号通路可能是关键通路。细胞实验也确定了karakoline和isotalatizidine能降低MC4R在阿霉素诱导的心肌损伤中的表达。结论附子可能通过调控MC4R调控阿霉素诱导的心肌损伤,同时也确定了MC4R在阿霉素诱导的心肌损伤中的作用,为阿霉素诱导的心肌损伤提供了新的治疗药物及治疗靶点。Objective To investigate the potential mechanism of Fuzi against adriamycin-induced myocardial injury by network pharmacology and cellular experiments.Methods The active compounds of adriamycin and Fuzi were identified and targets were predicted by TCMSP,SWISS,Chemal and Super-ped databases,and the targets of myocardial injury were predicted by Genecard database;the component-target network diagram was constructed by using Cytoscape 3.8.0 software;the PPI network diagram was constructed by using STRING database,and GO analysis and KEGG analysis were performed by using DAVID database.Molecular docking and molecular dynamics were used to verify the binding ability of the core targets and active compounds;finally,preliminary verification was carried out through cellular experiments.Results 2,7-Dideacetyl-2,7-dibenzoyl-taxayunnanine F,karakoline,and isotalatizidine may be the potential active compounds of Fuzi against adriamycin-induced myocardial injury,among which MAPK1,MAPK3 and MC4R may be potential targets of Fuzi against adriamycin-induced myocardial injury,and the neuroactive ligand-receptor interaction signaling pathway may be the key pathway.Cellular experiments also determined that karakoline and isotalatizidine reduced the expression of MC4R in adriamycin-induced myocardial injury.Conclusion Fuzi may regulate adriamycin-induced myocardial injury by modulating MC4R,and the role of MC4R in adriamycin-induced myocardial injury was also determined,providing a new therapeutic agent and a therapeutic target for adriamycin-induced myocardial injury.

关 键 词：附子 阿霉素 心肌损伤 网络药理学 分子动力学模拟 

分 类 号：R965[医药卫生—药理学]