基于网络药理学和分子对接探讨人参-红景天治疗心肌缺血/再灌注损伤的作用机制  

Mechanism of Ginseng-Rhodiola rosea in treatment of myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking

作　　者：赵倩琳 赖颖蓉 姜丽红[2] ZHAO Qian-lin;LAI Ying-rong;JIANG Li-hong(College of Traditional Chinese Medicine,Changchun University of Traditional Chinese Medicine,Changchun 130117,China;Affiliated Hospital of Changchun University of Traditional Chinese Medicine,Changchun 130021,China)

机构地区：[1]长春中医药大学中医学院,吉林长春130117 [2]长春中医药大学附属医院,吉林长春130021

出　　处：《中国药理学通报》2023年第5期970-978,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81673846);吉林省科技厅发展计划项目(No 20200201320JC)。

摘　　要：目的采用网络药理学方法、分子对接技术及实验研究,探究人参-红景天治疗心肌缺血/再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的作用靶点及机制。方法通过TCMSP数据库及文献补充筛选人参-红景天的有效活性成分及靶点,检索GENECARDS、DISGENET、DRUGBANK数据库得到MIRI靶点,使用STRING数据库构造功能蛋白相互作用网络(PPI),筛出核心靶点;并选择DAVID数据库进行基因本体功能分析(GO)和KEGG信号通路富集分析;最后借助分子对接技术及实验研究进行初步验证。结果获得人参-红景天有效活性成分43种,潜在靶点348个,并发现IL-6、TNF-α、VEGFA等靶点与MIRI密切相关,主要涉及TNF、PI3K-Akt、HIF-1等信号通路。分子对接结果显示,豆甾醇、人参皂苷rh2及红景天苷与IL-6、TNF-α、Caspase-3等靶点均有较好的结合作用且匹配度高,其中结合性最好的是Caspase-3与人参皂苷rh2,实验研究结果显示,人参-红景天可改善MIRI后心肌组织坏死,减轻心肌细胞水肿及血管充血情况,并降低MIRI大鼠中TNF-α及IL-6的表达水平。结论人参-红景天可能通过豆甾醇、人参皂苷rh2及红景天苷来调控IL-6、TNF-α、Caspase-3等多个靶点,抑制炎症及氧化应激反应,减轻心肌细胞损伤,发挥对MIRI的治疗作用。Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat-ment of myocardial ischemia-reperfusion injury(MIRI)via using network pharmacology approach,molecular docking techniques and experimental studies.Methods The active ingredients and targets of Ginseng-Rhodiola rosea were screened through the TCMSP database and literature supplementation,and the GENECARDS,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI.Functional protein interaction networks(PPIs)and the STRING database were used to screen out core targets.The DAVID database was also selected for gene ontology functional analysis(GO)and KEGG signaling pathway enrichment analysis.Lastly,the preliminary validation was performed with the help of molecular docking techniques and experimental studies.Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained,and targets such as IL-6,TNF-αand VEGFA were found to be closely related to MIRI,mainly involving TNF,PI3K-Akt,HIF-1 and other signaling pathways.The molecular docking results showed that soysterol,ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6,TNF-α,Caspase-3,VEGFA,MAPK1 and other targets,among which the best binding was between Caspase-3 and ginsenoside rh2.The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion,reduce myocardial cell edema and vascular congestion,and decrease the expression levels of TNF-αand IL-6 in MIRI rats.Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α,Caspase-3,VEGFA and MAPK1 through dousterol,ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress,reduce cardiomyocyte damage and exert therapeutic effects on MIRI.

关 键 词：人参-红景天 心肌缺血/再灌注损伤 网络药理学 分子对接 核心靶点 信号通路 

分 类 号：R282.71[医药卫生—中药学] R319[医药卫生—中医学] R364.5R349.1R542.2