基于网络药理学及实验验证探讨稳心汤治疗冠心病心绞痛的作用机制  

The Mechanism of Wenxin Decoction in Treating Coronary Heart Disease Angina Pectoris Based on Network Pharmacology and Experimental Verification

作　　者：白栋汉 谭雨晴 李军[1] 邵祯 陈恒文[1] BAI Donghan;TAN Yuqing;LI Jun;SHAO Zhen;CHEN Hengwen(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学研究生院,北京100029

出　　处：《中西医结合心脑血管病杂志》2023年第13期2383-2390,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81973836,82074396);首都卫生发展科研专项重点攻关项目(No.2020-1-4151);中国中医科学院“优势病种-医院制剂-新药”研发专项(No.ZZ15-XY-CT-08)。

摘　　要：目的:基于网络药理学探讨稳心汤治疗气虚血瘀型冠心病心绞痛的潜在作用靶点及其分子机制,并结合大鼠心肌梗死模型深入探析其可能的作用机制。方法:将中药系统药理学数据库和分析平台(TCMSP)获取的稳心汤中药物潜在相关靶点,与人类孟德尔遗传病数据库(OMIM)、药物数据库(DrugBank)、人类基因数据库(GeneCards)中筛选得到的冠心病心绞痛靶点取交集,并基于STRING数据库构建交集靶点蛋白互作网络图。根据Cytoscape 3.9.1软件构建稳心汤关键活性成分-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,筛选出稳心汤治疗气虚血瘀型冠心病心绞痛过程中可能参与的信号通路。构建大鼠心肌梗死模型,采用苏木精-伊红(HE)、马松(Masson)染色观察心脏炎症及纤维化情况,利用蛋白免疫印迹法(Western Blot)实验验证网络药理学富集分析结果。结果:共获取稳心汤与冠心病心绞痛交集靶点173个,包括白介素6(IL6)、肿瘤坏死因子(TNF)、丝氨酸/苏氨酸蛋白激酶(Akt1)等,KEGG富集信号通路205条,包括脂质和动脉粥样硬化、磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路等。HE、Masson染色显示,稳心汤可降低心肌梗死后心肌炎症反应,缓解纤维化进程。Western Blot实验显示,稳心汤可以升高PI3K/Akt蛋白表达水平(P<0.01)。结论:稳心汤可通过多成分、多靶点治疗冠心病心绞痛,其中可能与PI3K/Akt信号通路相关,为揭示稳心汤疗效的分子机制和生物学基础提供了有力依据,为进一步院内制剂的研发提供了新思路。Objective:To predict the potential molecular mechanism of Wenxin Decoction(WXT)in the treatment of coronary heart disease angina pectoris based on network pharmacology,and verify the results by myocardial infarction rat model.Methods:The potential targets of WXT were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the disease targets obtained from the Human Mendelian Inherited Diseases Database(OMIM),Drugbank,and GeneCards databases.The protein interaction network map of the intersected targets was constructed based on the STRING database.The network of"Key active ingredients of WXT-disease targets"was constructed according to Cytoscape 3.9.1,and the core targets were screened out.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of intersection targets was performed to screen out the possible signaling pathways using the Metascape platform.Then,rat myocardial infarction model was established.Cardiac inflammation and fibrosis were observed by hematoxylin-eosin(HE)staining and Masson staining.The possible pathways involved were verified by Western Blot experiments.Results:A total of 173 intersection targets of WXT and coronary heart disease angina pectoris were obtained,including interleukin-6(IL6),tumor necrosis factor(TNF),serine/threonine protein kinase(Akt1).KEGG pathway analysis screened out 205 related signaling pathways,including lipid,atherosclerosis,phosphatidylinosito-l 3-kinase(PI3K)/Akt signaling pathway,and mitogen activated protein kinase(MAPK)signaling pathway,etc.HE and Masson staining showed that WXT could reduce the myocardial inflammatory response after myocardial infarction and alleviate the fibrosis process.Western Blot experiments proved that WXT could affect the expression level of PI3K/Akt protein(P<0.01).Conclusion:WXT can treat coronary heart disease angina pectoris through multiple components and targets,which may be related to PI3K/Akt signaling pathway,and provide effective basis for reveal

关 键 词：冠心病心绞痛 稳心汤 网络药理学 实验验证 作用机制 

分 类 号：R285[医药卫生—中药学]