基于网络药理学和实验验证研究丹参饮治疗心衰的作用机制  

Mechanism of DanShenyin in heart failure based on network pharmacology and experimental validation

作　　者：王晶[1] 李莉[1] 刘冰 周昆[1,2] 于英莉 WANG Jing;LI Li;LIU Bing;ZHOU Kun;YU Ying-li(Center of Drug Safety Evaluation,Tianjin University of traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Component-based Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学药物安全评价中心,天津301617 [2]省部共建组分中药国家重点实验室,天津301617

出　　处：《中国药理学通报》2024年第9期1773-1780,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82204669)。

摘　　要：目的用网络药理学方法及体外实验验证,研究丹参饮(Danshenyin,DSY)治疗心衰的药理作用并探讨治疗机制。方法使用中药系统药理学分析平台(TCMSP),UniProt等数据库筛选丹参饮的有效成分及作用靶点,以“heart failure”为关键词检索Gene Cards等数据库得到疾病靶点,二者交集得到核心靶点。用STRING数据库构建核心靶点蛋白质-蛋白质相互作用网络,利用DAVID数据库进行生物功能和信号通路富集分析。构建“药材-成分-靶点-疾病”网络,将活性成分与靶点分子对接验证。手术结扎小鼠心脏冠状动脉左前降支建立心衰模型,丹参饮干预,超声检测、蛋白免疫印记对预测结果进行实验验证。结果网络药理学分析显示,丹参饮通过丹参醛、丹参酮ⅡA、miltiononeⅡ等成分发挥对心衰的治疗作用,其作用机制可能与参与MAPK信号级联的生物调控过程以及调控MAPK等信号通路相关;动物实验对这一发现进行了初步验证:实验发现丹参饮治疗后小鼠左心室心功能、流出道血流等超声指标得到改善;心肌组织中MAPK信号通路蛋白ERK、JNK、p38磷酸化水平降低(P<0.05)。结论丹参饮能够保护心肌,影响MAPK通路从而发挥对慢性心衰的治疗作用。Aim To investigate the pharmacological effects of Danshenyin(DSY)in treating heart failure using network pharmacology and in vitro experiments.Methods Utilizing the Traditional Chinese Medicine Systems Pharmacology Analysis Platform(TCMSP),UniProt and other databases,active components and targets of DSY were analyzed.Disease-related targets were identified via searches in the Gene Cards and other databases using keyword“heart failure”.Subsequently,the intersection of DSY and heart failure targets was conducted to obtain core targets.The STRING database was employed to construct a protein-protein interaction(PPI)network,and biological function and signal pathway enrichment analysis were performed using the DAVID database.Establish a network of“medicinal materials-ingredients-target-disease.”According to this network,a preliminary docking validation of the active ingredient with the target molecule.A mouse model of chronic heart failure was established through left anterior descending coronary artery ligation,with prediction results confirmed via echocardiographic detection and Western blotting.Results Network pharmacological analysis indicated that DSY may regulate the MAPK cascade signaling pathway via pharmacological components such as danshenyin aldehyde,luteolin,tanshinone A,and miltiononeⅡto treat heart failure.Animal experiments demonstrated significant improvements in ultrasound indexes like left ventricular cardiac function and outflow tract blood flow in the DSY treatment group compared to the model group(P<0.05).Additionally,myocardial tissue phosphorylation levels of ERK,JNK,and p38 were significantly reduced(P<0.05).Conclusion DSY protects the myocardium,influences the MAPK pathway,and holds promise for treating chronic heart failure.

关 键 词：丹参饮 心力衰竭 网络药理学 超声 作用机制 分子对接 

分 类 号：R-332[医药卫生] R289.5R319R541.61