基于网络药理学的丹红注射液改善阿司匹林抵抗机制分析
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摘要
该文利用网络药理学理念和网络分析技术,拟探讨丹红注射液改善阿司匹林抵抗的潜在活性成分和可能作用机制。利用TCMSP平台收集丹参和红花的主要活性成分和作用靶点信息,就拓扑学特征对丹红注射液的活性成分进一步筛选,选取节点自由度≥9的活性成分作为主要活性成分;从Gene Cards数据库获取与阿司匹林抵抗相关的基因靶点,采用Cytoscape3. 7. 0构建药物-活性成分-靶点-疾病网络,并用FunRich 3. 1. 3软件进行基因富集分析。共获得丹红注射液活性成分110个,经筛选得到主要活性成分共60个,其中丹参成分51个,红花成分11个,丹参、红花共有成分2个;收集到靶点基因159个。基因富集分析结果显示,丹红注射液主要通过涉及凝血过程、炎症反应、代谢调节的21条通路改善阿司匹林抵抗。该研究基于网络药理学方法,揭示了丹红注射液从凝血过程、炎症反应、代谢调节等途径多成分、多靶点、多通路改善阿司匹林抵抗的作用,为后续研究开展实验工作提供了更丰富的信息和依据。
This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.
This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.
引文
[1]韩雅玲.冠心病阿司匹林抵抗的研究与对策[J].中国实用内科杂志,2015,35(1):3.
[2] Krasopoulos G,Brister S J,Beattie W S,et al. Aspirin"resistance"and risk of cardiovascular morbidity:systematic review and meta-analysis[J]. BMJ,2008,336(7637):195.
[3]薛梅,薛丽娜,史大卓.阿司匹林抵抗中西医结合防治进展与展望[J].中国中西医结合杂志,2014,34(2):245.
[4]张翠英,任伟光.基于经典丹参药对“丹参-冰片”、“丹参-红花”的药动学研究探讨中药配伍增效的药动学研究策略[J].中国中药杂志,2017,42(12):2413.
[5]王赏,卢宏.丹红注射液的临床研究进展[J].中国实用神经疾病杂志,2018,21(17):1862.
[6]李建萍.丹红注射液与阿司匹林药物相互作用特征与机制研究[D].南京:南京中医药大学,2017.
[7]汪元元,徐全胜.丹红注射液对冠心病患者阿司匹林抗血小板作用及胃黏膜损伤的影响[J].山东医药,2018,58(34):44.
[8]王勇,孔丽君,王胜煌,等.丹红注射液对冠心病患者阿司匹林反应单位和临床预后的影响[J].中华中医药学刊,2017,35(5):1243.
[9]沈乐.阿司匹林抵抗相关因素分析及丹红注射液干预研究[D].南京:南京中医药大学,2017.
[10]任钧国,刘建勋.中药注射剂上市后作用机制研究的思路与方法[J].中国现代中药,2018,20(11):1319.
[11] Ru J L,Li P,Wang J N,et al. TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminformatics,2014,6(1):13.
[12] Yang H,Zhang W,Huang C,et al. A novel systems pharmacology model for herbal medicine injection:a case using reduning injection[J]. BMC Complement Alter Med,2014,14(1):430.
[13] Shannon P,Markiel A,Ozier O,et al. Cytoscape:a software environment for integrated models of biomolecular interaction networks[J]. Genome Res,2003,13(11):2498.
[14] Pathan M,Keerthikumar S,Chisanga D,et al. A novel community driven software for functional enrichment analysis of extracellular[J]. J Extracell Vesicles,2017,6(1):1321455.
[15] Floyd C N,Ferro A. Mechanisms of aspirin resistance[J]. Pharmacol Therapeut,2014,141(1):69.
[16]刘晴晴,姜昆,陈晓虎.阿司匹林联合活血化瘀类中药对阿司匹林抵抗疗效的Meta分析[J].云南中医学院学报,2016,39(1):54.
[17]刘玥,殷惠军,史大卓,等.活血化瘀中药与抗血小板治疗[J].科学通报,2014,59(8):647.
[18]陈淑华,岳蕴华,马艳婷.阿司匹林代谢基因在心脑血管疾病治疗中的价值[J].临床检验杂志:电子版,2018,7(1):162.
[19] Du G,Lin Q,Wang J. A brief review on the mechanisms of aspirin resistance[J]. Int J Cardiol,2016,220:21.
[20] Larsen S B,Grove E L,Kristensen S D,et al. Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary artery disease[J]. Thromb Haemost,2013,109(5):920.
[21] Maione F,De Feo V,Caiazzo E,et al. TanshinoneⅡA,a major component of Salvia milthorriza Bunge,inhibits platelet activation via Erk-2 signaling pathway[J]. J Ethnopharmacol,2014,155(2):1236.
[22] Voyvodic P L,Min D,Liu R,et al. Loss of syndecan-1 induces a pro-inflammatory phenotype in endothelial cells with a dysregulated response to atheroprotective flow[J]. J Biol Chem,2014,289(14):9547.
[23]刘益臻,冯伟勋,付坤飞.运脾逐湿汤治疗湿热困脾型高血压代谢综合征[J].中国实验方剂学杂志,2017,23(19):196.
[24] Albert S G,Hasnain B I,Ritter D G,et al. Aspirin sensitivity of platelet aggregation in diabetes mellitus[J]. Diabetes Res Clin Pract,2005,70(2):195.
[25] Anfossi G,Russo I,Trovati M. Platelet dysfunction in central obesity[J]. Nutr Metab Cardiovasc Dis,2009,19(6):440.
[26] Kobzar G,Mardla V,Samel N. Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway but does not impair it through thromboxane A2receptors[J]. Prostaglandins Other Lipid Mediat,2017,131:33.
[27] SaraF,Saydam G,Sahin F,et al. Effects of hormone replacement therapy on insulin resistance and platelet function tests[J].Med Princ Pract,2009,18(1):43.
[2] Krasopoulos G,Brister S J,Beattie W S,et al. Aspirin"resistance"and risk of cardiovascular morbidity:systematic review and meta-analysis[J]. BMJ,2008,336(7637):195.
[3]薛梅,薛丽娜,史大卓.阿司匹林抵抗中西医结合防治进展与展望[J].中国中西医结合杂志,2014,34(2):245.
[4]张翠英,任伟光.基于经典丹参药对“丹参-冰片”、“丹参-红花”的药动学研究探讨中药配伍增效的药动学研究策略[J].中国中药杂志,2017,42(12):2413.
[5]王赏,卢宏.丹红注射液的临床研究进展[J].中国实用神经疾病杂志,2018,21(17):1862.
[6]李建萍.丹红注射液与阿司匹林药物相互作用特征与机制研究[D].南京:南京中医药大学,2017.
[7]汪元元,徐全胜.丹红注射液对冠心病患者阿司匹林抗血小板作用及胃黏膜损伤的影响[J].山东医药,2018,58(34):44.
[8]王勇,孔丽君,王胜煌,等.丹红注射液对冠心病患者阿司匹林反应单位和临床预后的影响[J].中华中医药学刊,2017,35(5):1243.
[9]沈乐.阿司匹林抵抗相关因素分析及丹红注射液干预研究[D].南京:南京中医药大学,2017.
[10]任钧国,刘建勋.中药注射剂上市后作用机制研究的思路与方法[J].中国现代中药,2018,20(11):1319.
[11] Ru J L,Li P,Wang J N,et al. TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminformatics,2014,6(1):13.
[12] Yang H,Zhang W,Huang C,et al. A novel systems pharmacology model for herbal medicine injection:a case using reduning injection[J]. BMC Complement Alter Med,2014,14(1):430.
[13] Shannon P,Markiel A,Ozier O,et al. Cytoscape:a software environment for integrated models of biomolecular interaction networks[J]. Genome Res,2003,13(11):2498.
[14] Pathan M,Keerthikumar S,Chisanga D,et al. A novel community driven software for functional enrichment analysis of extracellular[J]. J Extracell Vesicles,2017,6(1):1321455.
[15] Floyd C N,Ferro A. Mechanisms of aspirin resistance[J]. Pharmacol Therapeut,2014,141(1):69.
[16]刘晴晴,姜昆,陈晓虎.阿司匹林联合活血化瘀类中药对阿司匹林抵抗疗效的Meta分析[J].云南中医学院学报,2016,39(1):54.
[17]刘玥,殷惠军,史大卓,等.活血化瘀中药与抗血小板治疗[J].科学通报,2014,59(8):647.
[18]陈淑华,岳蕴华,马艳婷.阿司匹林代谢基因在心脑血管疾病治疗中的价值[J].临床检验杂志:电子版,2018,7(1):162.
[19] Du G,Lin Q,Wang J. A brief review on the mechanisms of aspirin resistance[J]. Int J Cardiol,2016,220:21.
[20] Larsen S B,Grove E L,Kristensen S D,et al. Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary artery disease[J]. Thromb Haemost,2013,109(5):920.
[21] Maione F,De Feo V,Caiazzo E,et al. TanshinoneⅡA,a major component of Salvia milthorriza Bunge,inhibits platelet activation via Erk-2 signaling pathway[J]. J Ethnopharmacol,2014,155(2):1236.
[22] Voyvodic P L,Min D,Liu R,et al. Loss of syndecan-1 induces a pro-inflammatory phenotype in endothelial cells with a dysregulated response to atheroprotective flow[J]. J Biol Chem,2014,289(14):9547.
[23]刘益臻,冯伟勋,付坤飞.运脾逐湿汤治疗湿热困脾型高血压代谢综合征[J].中国实验方剂学杂志,2017,23(19):196.
[24] Albert S G,Hasnain B I,Ritter D G,et al. Aspirin sensitivity of platelet aggregation in diabetes mellitus[J]. Diabetes Res Clin Pract,2005,70(2):195.
[25] Anfossi G,Russo I,Trovati M. Platelet dysfunction in central obesity[J]. Nutr Metab Cardiovasc Dis,2009,19(6):440.
[26] Kobzar G,Mardla V,Samel N. Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway but does not impair it through thromboxane A2receptors[J]. Prostaglandins Other Lipid Mediat,2017,131:33.
[27] SaraF,Saydam G,Sahin F,et al. Effects of hormone replacement therapy on insulin resistance and platelet function tests[J].Med Princ Pract,2009,18(1):43.