基于网络药理学探讨参夏合剂治疗冠心病的通路及机制研究
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摘要
目的基于网络药理学探讨参夏合剂治疗冠心病的主要作用通路与可能机制。方法通过网络药理学和生物信息学方法进行研究。结果首先检索参夏合剂中的药物中已知活性成分727个,并根据其有效成分的口服利用度等条件进行筛选获得关键入血活性成分109个,得到对应基因的相应靶点1880个,然后再挖掘筛选冠状动脉粥样硬化性心脏病的已知发病密切相关的基因靶点228个,将药物与疾病靶点取交集进行分析,筛选出参夏合剂与冠状动脉粥样硬化性心脏病的相关性最强的特异性关键基因94个,采用Clue Go进行信号通路富集分析,显示参夏合剂作用于冠状动脉粥样硬化性心脏病的关键节点涉及的信号通路主要被富集在P53类介质对信号转导的调节作用、细胞周期调控、EB病毒感染、凋亡、DNA切除与修复等数十条信号通路。结论网络药理学分析显示,参夏合剂理论上对于冠状动脉粥样硬化性心脏病的治疗确实有着非常高的针对性,表现在其可从多个重要通路进行疾病干预,且具有多成分、多靶点的特点。分析其主要通路可发现参夏合剂的治疗作用覆盖了冠状动脉粥样硬化性心脏病发病的主要过程。
Objective To explore the pathway and the mechanism of shenxia mixture in the treatment of coronary atherosclerotic cardiopathy based on the network pharmacology. Methods The network pharmacology and bioinformatics were adopted. Results A total of 727 known active components were retrieved from shenxia mixture. According to the utility of the effective component in oral administration,109 active components that act on the blood system were screened specially and 1880 corresponding genetic targets were obtained. Afterwards,228 genetic targets closely related to coronary atherosclerotic cardiopathy were mined. The intersection between the drug and disease targets was analyzed and 94 specific key genes were screened in terms of the strongest correlation between shenxia mixture and coronary atherosclerotic cardiopathy. Using ClueG o,the signal pathway enrichment was analyzed. It was shown that the signal pathway involved in the key actions of shenxia mixture on coronary atherosclerotic cardiopathy was enriched on the regulating effect of P53 media on the signal transduction,cell cycle control,EB virus infection,apoptosis,DNA excision and repair,etc. Conclusion The network pharmacology analysis shows that shenxia mixture presents very highly effects on coronary atherosclerotic cardiopathy in theory,manifested as the intervention to the disease through different important approaches and characterized as multi-components and multi-targets. It is discovered that the therapeutic effects of shenxia mixture cover the main pathogenic process of coronary atherosclerotic cardiopathy.
Objective To explore the pathway and the mechanism of shenxia mixture in the treatment of coronary atherosclerotic cardiopathy based on the network pharmacology. Methods The network pharmacology and bioinformatics were adopted. Results A total of 727 known active components were retrieved from shenxia mixture. According to the utility of the effective component in oral administration,109 active components that act on the blood system were screened specially and 1880 corresponding genetic targets were obtained. Afterwards,228 genetic targets closely related to coronary atherosclerotic cardiopathy were mined. The intersection between the drug and disease targets was analyzed and 94 specific key genes were screened in terms of the strongest correlation between shenxia mixture and coronary atherosclerotic cardiopathy. Using ClueG o,the signal pathway enrichment was analyzed. It was shown that the signal pathway involved in the key actions of shenxia mixture on coronary atherosclerotic cardiopathy was enriched on the regulating effect of P53 media on the signal transduction,cell cycle control,EB virus infection,apoptosis,DNA excision and repair,etc. Conclusion The network pharmacology analysis shows that shenxia mixture presents very highly effects on coronary atherosclerotic cardiopathy in theory,manifested as the intervention to the disease through different important approaches and characterized as multi-components and multi-targets. It is discovered that the therapeutic effects of shenxia mixture cover the main pathogenic process of coronary atherosclerotic cardiopathy.
引文
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[2]宋鲁成,相宏杰.参夏合剂对动脉粥样硬化大鼠血脂和主动脉平滑肌细胞凋亡的影响[J].陕西中医,2014,35(2):242-243.
[3]宋鲁成,相宏杰.参夏合剂影响AngⅡ诱导大鼠胸主动脉血管平滑肌细胞凋亡和Caspase-3表达的研究[J].四川中医,2013,31(10):39-40.
[4]杨文笑,宋鲁成.参夏合剂加味治疗PCI术后再发心绞痛临床体会[J].中医临床研究,2016,8(7):84-85.
[5]张守芳.参夏加桂合剂治疗冠心病稳定型心绞痛的临床疗效观察[D].济南:山东中医药大学,2016.
[6]张琛.益气化积方治疗经皮冠状动脉介入治疗(PCI)术后心绞痛的临床观察观察[D].济南:山东中医药大学,2014.
[7]Li Y,Zhang J,Zhang L,et al. Systems pharmacology to decipher thecombinational anti-migraine effects of Tianshu formula[J]. J Ethno-pharmacol,2015,174:45-56.(下转第28页)
[8]Huang L,Xie D,Yu Y,et al. TCMID 2. 0:a comprehensive resourcefor TCM[J]. Nucleic Acids Res,2018,46(D1):D1117-D1120.
[9]Liu H,Wang J,Zhou W,et al. Systems approaches and polypharma-cology for drug discovery from herbal medicines:an example using lic-orice[J]. J Ethnopharmacol,2013,146(3):773-793.
[10]Xu X,Zhang W,Huang C,et al. A novel chemometric method forthe prediction of human oral bioavailability[J]. Int J Mol Sci,2012,13(6):6964-6982.
[11]Ma C,Wang L,Xie XQ. GPU accelerated chemical similarity calcu-lation for compound library comparison[J]. J Chem Inf Model,2011,51(7):1521-1527.
[12]Li J,Zhao P,Li Y,et al. Systems pharmacology-based dissection ofmechanisms of Chinese medicinal formula Bufei Yishen as an effec-tive treatment for chronic obstructive pulmonary disease[J]. SciRep,2015,5:15290.
[13]Shannon P,Markiel A,Ozier O,et al. Cytoscape:a software environ-ment for integrated models of biomolecular interaction networks[J].Genome Res,2003,13(11):2498-2504.
[14]Ma Q,Lu AY. Pharmacogenetics,pharmacogenomics,and individu-alized medicine[J]. Pharmacol Rev,2011,63(2):437-459.
[15]Hamosh A,Scott AF,Amberger JS,et al. Online Mendelian Inherit-ance in Man(OMIM),a knowledgebase of human genes and geneticdisorders[J]. Nucleic Acids Res,2005,33(Database issue):D514-D517.
[16]Wishart DS,Knox C,Guo AC,et al. DrugBank:a knowledgebase fordrugs,drug actions and drug targets[J]. Nucleic Acids Res,2008,36(Database issue):D901-D906.
[17]Liu X,Zhu F,Ma X,et al. The Therapeutic Target Database:an in-ternet resource for the primary targets of approved,clinical trial andexperimental drugs[J]. Expert Opin Ther Targets,2011,15(8):903-912.
[18]Robinson PN,Mundlos S. The human phenotype ontology[J]. ClinGenet,2010,77(6):525-534.
[19]Tang Y,Li M,Wang J,et al. CytoNCA:a cytoscape plugin for cen-trality analysis and evaluation of protein interaction networks[J].Biosystems,2015,127:67-72.
[20]Bindea G,Mlecnik B,Hackl H,et al. ClueGO:a Cytoscape plug-into decipher functionally grouped gene ontology and pathway annota-tion networks[J]. Bioinformatics,2009,25(8):1091-1093.
[21]He J,Gu D,Wu X,et al. Major causes of death among men andwomen in China[J]. N Engl J Med,2005,353(11):1124-1134.