基于网络药理学和生物信息学的丹参酮Ⅱ_A治疗冠心病的分子生物学机制分析
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摘要
目的基于网络药理学和生物信息学方法分析丹参酮Ⅱ_A治疗冠心病(CHD)的分子生物学机制。方法利用Pharm Mapper数据库筛选出丹参酮Ⅱ_A的作用靶点,利用OMIM、GeneCards、CTD数据库筛选CHD疾病作用相关靶点。利用STRING数据库进行蛋白互作网络分析,利用Cytoscape构建蛋白相互作用网络,利用ClueGO插件进行GO分析和KEGG信号通路富集分析,利用Systemsdock数据库进行系统分子对接,利用i GEMDOCK软件进行分子对接来预测丹参酮Ⅱ_A对CHD作用靶点的结合性。结果筛选出丹参酮Ⅱ_A的潜在靶点173个;与CHD相关的靶点42个;信号通路49条。结论丹参酮Ⅱ_A治疗CHD具有多靶点、多通路作用的特点;其可能作用机制是通过调控CHD发展过程中的血压调节、细胞代谢、血管新生、内分泌、活性氧代谢等过程对CHD进行干预。
Objective To analyze the molecular biological mechanism of tanshinone Ⅱ_A in the treatment of coronary heart disease(CHD) based on network pharmacology and bioinformatics methods. Methods The targets of tanshinone Ⅱ_A were screened by uploading the chemical structure to PharmMapper database. Related targets of CHD were screened by OMIM, GeneCards, and CTD databases. The above data were imported into STRING database for PPI network analysis. Protein interaction network was constructed using Cytoscape. Gene Ontology analysis and enrichment analysis of KEGG signaling pathway were performed by Cluego. Systemsdock database was used for system molecular docking, and iGEMDOCK software was used for molecular docking to test the binding of tanshinone Ⅱ_A to the targets of coronary heart disease. Results A total of 173 possible potential targets of tanshinone Ⅱ_A, 42 targets related to CHD and 49 signal pathways were identified. Conclusion Tanshinone Ⅱ_A has the characteristics of multi-target and multi-pathway in the treatment of CHD, and its mechanism may be through the regulation of blood pressure, cell metabolism, angiogenesis, endocrine, reactive oxygen metabolism, and other bioprocesses during the development of CHD.
Objective To analyze the molecular biological mechanism of tanshinone Ⅱ_A in the treatment of coronary heart disease(CHD) based on network pharmacology and bioinformatics methods. Methods The targets of tanshinone Ⅱ_A were screened by uploading the chemical structure to PharmMapper database. Related targets of CHD were screened by OMIM, GeneCards, and CTD databases. The above data were imported into STRING database for PPI network analysis. Protein interaction network was constructed using Cytoscape. Gene Ontology analysis and enrichment analysis of KEGG signaling pathway were performed by Cluego. Systemsdock database was used for system molecular docking, and iGEMDOCK software was used for molecular docking to test the binding of tanshinone Ⅱ_A to the targets of coronary heart disease. Results A total of 173 possible potential targets of tanshinone Ⅱ_A, 42 targets related to CHD and 49 signal pathways were identified. Conclusion Tanshinone Ⅱ_A has the characteristics of multi-target and multi-pathway in the treatment of CHD, and its mechanism may be through the regulation of blood pressure, cell metabolism, angiogenesis, endocrine, reactive oxygen metabolism, and other bioprocesses during the development of CHD.
引文
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[2]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017》概要[J].中国循环杂志,2018,33(1):1-8.
[3]乔高红.丹参酮ⅡA磺酸钠注射液联合门冬胰岛素30注射液治疗糖尿病肾病的疗效观察[J].现代药物与临床,2018,33(9):2403-2408.
[4]黄坤,陈伟伟,刘锐,等.基于生物信息学方法分析复方苦参注射液治疗肝癌的分子生物学机制[J].山西医科大学学报,2018,49(9):1013-1019.
[5]李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[6]杨倩,吕莉莉,孙蓉.基于网络药理学的丹参川芎嗪注射液作用机制分析[J].中草药,2018,49(11):2606-2613.
[7]Zhang Y Q,Mao X,Guo Q Y,et al.Network pharmacology-based approaches capture essence of Chinese herbal medicines[J].Chin Herb Med,2016,8(2):107-116.
[8]Liu X,Ouyang S,Yu B,et al.PharmMapper server:Aweb server for potential drug target identification using pharmacophore mapping approach[J].Nucleic Acids Res,2010,38(web server issue):W609-W614.
[9]Wang X,Pan C,Gong J,et al.Enhancing the enrichment of pharmacophore-based target prediction for the polypharmacological profiles of drugs[J].J Chem Inf Model,2016,56(6):1175-1183.
[10]Wang X,Shen Y,Wang S,et al.Pharm Mapper 2017update:A web server for potential drug target identification with a comprehensive target pharmacophore database[J].Nucleic Acids Res,2017,45(W1):W356-W360.
[11]刘鑫馗,吴嘉瑞,张丹,等.基于网络药理学的生脉散作用机制分析[J].中国实验方剂学杂志,2017,23(16):219-226.
[12]林昶,杨欣,朱璨,等.新疆红花挥发油GC-MS分析及药理作用的分子机制[J].中国实验方剂学杂志,2018,24(23):104-111.
[13]Hsin K Y,Ghosh S,Kitano H.Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J].PLo S One,2013,8(12):e83922.
[14]王冠男,李勇,张健,等.美托洛尔联合胺碘酮治疗冠心病合并心律失常的临床疗效观察[J].中华老年心脑血管病杂志,2018,20(9):932-935.
[15]胡黎文,余国辉,杜怡雯,等.冠心病心绞痛的中医药治疗研究进展[J].湖南中医杂志,2018,34(5):183-185.
[16]资润.中西医结合治疗慢性稳定型心绞痛的临床研究[D].北京:北京中医药大学,2008.
[17]王月鹏.丹参酮ⅡA磺酸钠联合氯吡格雷辅治不稳定型心绞痛临床疗效观察[J].中医临床研究,2015,7(2):97-98.
[18]何薇,石元龙,郑成根.丹参酮ⅡA磺酸钠联合辛伐他汀治疗冠心病心绞痛的临床研究[J].中国临床药理学杂志,2016,32(5):393-395.
[19]Agbor L N,Wiest E F,Rothe M,et al.Role of CYP1A1in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids[J].J Pharmacol Exp Ther,2014,351(3):688-698.
[20]Guessous I,Dobrinas M,Kutalik Z,et al.Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension[J].Hum Mol Genet,2012,21(14):3283-3292.
[21]潘晔,殷佳,蔡雪朦,等.基于PI3K/Akt信号通路探讨中医药治疗冠心病的研究进展[J].中草药,2017,48(19):4100-4104.
[22]窦梦怡,秦富忠,李保.缺氧诱导因子在心脏重构和心力衰竭中的作用[J].中国循环杂志,2015,30(11):1125-1127.
[23]Sano M,Minamino T,Toko H,et al.p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload[J].Nature,2007,446(7134):444-448.
[24]周茜,张敏芳,任海燕,等.硫化氢干预对小鼠心肌纤维化MAPK通路表达的影响[J].中国老年学杂志,2018,38(12):2981-2984.
[25]罗永苗,陈朝俊,李玥珺.基于NF-κB探讨参七脉心通胶囊抗动脉粥样硬化的作用机制[J].西部中医药,2018,31(5):8-10.
[26]吕宏娟,康晓敏.Toll样受体2在血管紧张素Ⅱ致高血压小鼠心肌纤维化中的作用[J].中华老年心脑血管病杂志,2014,16(8):860-862.
[27]和凡,钟国平,赵立子,等.丹参酮ⅡA对大鼠细胞色素P450酶的诱导作用[J].中草药,2009,40(6):938-942.