摘要
目的:采用小鼠阿霉素心脏毒性模型验证郭维琴教授益气泻肺汤加减方对阿霉素心脏毒性的干预作用,运用网络药理学方法探讨益气泻肺汤加减方干预阿霉素心脏毒性的作用机制。方法:构建小鼠阿霉素心脏毒性模型,采用酶联免疫吸附法(ELISA)检测心肌肌钙蛋白T(cTnT)评估心肌损伤程度,采用苏木精-伊红(HE)染色、马松(Masson)染色观察心脏炎症及纤维化情况。通过中药系统药理学数据库和分析平台(TCMSP)获取益气泻肺汤加减方中药物潜在相关靶点,与人类孟德尔遗传在线数据库(OMIM)、药物数据库(DrugBank)、基因名片数据库(GeneCards)中筛选得到的阿霉素心脏毒性靶点取交集,并基于STRING数据库构建交集靶点蛋白互作网络图。根据Cytoscape 3.10.1软件构建益气泻肺汤加减方关键活性成分-疾病靶点网络,筛选出核心靶点。利用Metascape平台对药物与疾病交集靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析,筛选出益气泻肺汤加减方治疗阿霉素心脏毒性过程中可能参与的信号通路。结果:动物实验结果显示,益气泻肺汤加减方可以减少心肌组织中的炎性细胞浸润以及胶原纤维沉积,降低cTnT水平,明显改善心肌损伤,有效干预阿霉素心脏毒性。网络药理学结果显示,益气泻肺汤加减方中10种药物共130种化学成分,作用于1216个基因靶点,其中,黄芪、葶苈子、桑白皮、红花、车前子为发挥作用的核心药物,槲皮素、山柰酚、木犀草素、黄芩苷、丹参酮ⅡA等为复方中主要化合物,蛋白激酶B(AKT)1、肿瘤抑制蛋白(TP53)、转录激活因子3(STAT3)、肿瘤坏死因子(TNF)等为关键靶点,主要通过脂质与动脉粥样硬化、TNF信号通路、坏死等作用通路干预阿霉素心脏毒性。结论:益气泻肺汤加减方干预阿霉素心脏毒性的作用机制涉及多成分、多靶点、多通路。
Objective:To verify the intervention effect of Professor Guo Weiqin Yiqi Xifei Decoction on doxorubicin cardiotoxicity by network pharmacology.Methods:Rat model of doxorubicin induced cardiotoxicity were constructed.Cardiac troponin T(cTnT)was detected by enzyme-linked immunosorbent assay(ELISA)to evaluate myocardial injury.Hematoxylin-eosin(HE)and Masson staining were used to observe cardiac inflammation and fibrosis.Potential drug related targets in Yiqi Xifei Decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the doxorubicin cardiotoxic targets screened from human Menelian Genetics online database(OMIM),drug database(DrugBank)and gene card database(GeneCards).The intersection target protein interaction network diagram was constructed based on STRING database.According to Cytoscape 3.10.1 software,the disease target network,which was the key active ingredient of Yiqi Xifei Decoction,was constructed,and the core targets were screened.The gene ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were enriched for the intersection targets of drugs and diseases using Metascape platform,and the possible signal pathways involved in the treatment of doxorubicin induced cardiotoxicity by Yiqi Xifei Decoction were screened.Results:The results of animal experiments showed that Yiqi Xifei Decoction could reduce inflammatory cell infiltration and collagen fiber deposition in myocardial tissue,reduce cTnT level,significantly improve myocardial injury,and effectively intervene doxorubicin induced cardiotoxicity.The network pharmacological results showed that there were 130 chemical components of 10 drugs in Yiqi Xifei Decoction,which acted on 1216 gene targets.Huangqi(Radix Scutellariae),Tinglizi(Lyocarpa),Sangbaipi(Cortex Mori),Honghua(Carthamus tinctorius),and Cheqianzi(Plantain seed)were the core drugs.Quercetin,kaempferol,luteolin,baicalin and tanshinoneⅡA were the main compounds.Protein kinase B(AKT)1,tumor suppressor protein(TP53
作者
潘熠
林谦
魏兰
张立晶
李蒙
PAN Yi;LIN Qian;WEI Lan;ZHANG Lijing;LI Meng(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100070,China)
出处
《中西医结合心脑血管病杂志》
2024年第21期3850-3858,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
北京中医药大学“揭榜挂帅”项目(No.2023-JYB-JBZD-002)。
