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1.湖北中医药大学,武汉 430065
2.中国中医科学院 广安门医院,北京 100053
3.陕西中医药大学,陕西 咸阳 712083
[第一作者] 关庆亚,在读博士,从事伤寒论辨证论治及方药研究,E-mail:728887482@qq.com
*王阶,博士,主任医师,从事心血管疾病的中西医结合研究,E-mail:wangjie0103@126.com
收稿日期:2019-06-12,
网络出版日期:2019-10-17,
纸质出版日期:2020-03-05
移动端阅览
关庆亚, 王阶, 张云, 等. 基于网络药理学的小陷胸汤治疗冠心病作用机制[J]. 中国实验方剂学杂志, 2020,26(5):152-161.
Qing-ya GUAN, Jie WANG, Yun ZHANG, et al. Network Pharmacology-based Mechanism of Xiao Xianxiongtang in Treatment of Coronary Heart Disease[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(5): 152-161.
关庆亚, 王阶, 张云, 等. 基于网络药理学的小陷胸汤治疗冠心病作用机制[J]. 中国实验方剂学杂志, 2020,26(5):152-161. DOI: 10.13422/j.cnki.syfjx.20200322.
Qing-ya GUAN, Jie WANG, Yun ZHANG, et al. Network Pharmacology-based Mechanism of Xiao Xianxiongtang in Treatment of Coronary Heart Disease[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(5): 152-161. DOI: 10.13422/j.cnki.syfjx.20200322.
目的:
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通过网络药理学方法预测小陷胸汤治疗冠心病靶标并分析其作用特征,构建“成分-靶标-通路”网络药理模型,揭示小陷胸汤治疗冠心病的潜在通路机制。
方法:
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中药系统药理学数据库与分析平台(TCMSP)获得药物有效成分,Swiss靶标预测数据库(Swiss Target Prediction)反向药效团匹配法预测“小陷胸汤-冠心病”靶标;治疗靶标数据库(TTD),Drugbank,疾病-基因网数据库(DisGeNET)取美国食品和药物管理局(FDA)批准的冠心病并集靶标。韦恩图获得相关交集,GEO2R在线分析靶标特征,Funrich version 3软件分析生物过程,运用插件Reactome FI对靶标通路富集分析,采用Cytoscape软件构建“成分-靶标-通路”网络。
结果:
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网络分析表明,小陷胸汤治疗冠心病是通过25个治疗成分调控24个靶标,通过GEO2R在线多个基因芯片分析,靶标存在上下调差异,上调靶标11个,下调靶标13个,作用于4大生物过程,21条具体通路。
结论:
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小陷胸汤治疗冠心病的机制可能是通过黄连生物碱类和黄酮类、半夏的核苷类和有机酸类、瓜蒌的豆甾醇类和黄酮类参与基因表达、新陈代谢、蛋白质代谢等生物过程,调节相关靶蛋白的基因表达,调控基因转录通路、生物氧化反应和脂类和脂蛋白代谢、胰岛素样生长因子结合蛋白(IGFBPs)对胰岛素样生长因子(IGF)转运和摄取、细胞外基质的降解等信号通路。
Objective:
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To predict Xiao Xianxiongtang's treatment of coronary heart disease (CHD) targets and analyze their function by the network pharmacology method
and build ingredients-targets-channel network pharmacological model
in order to reveal potential pathways and mechanisms of Xiao Xianxiongtang for CHD treatment.
Method:
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Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain components
and CHD targets over Xiao Xianxiongtang were predicted by using Swiss Target Prediction reverse pharmacophore matching method. CHD targets which Food and Drug Administration (FDA) approved were collected from Therapeutic Target Database (TTD)
Drugbank and Disease-gene Net databases (DisGeNET). Wenn diagram was used to obtain the correlation intersection.Target characteristics were analyzed with GEO2R online
Reactome FI was used to analyze the enrichment of target pathways
and Cytoscape software was used to construct the " component-target-pathway" network.
Result:
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Network analysis showed that Xiao Xianxiongtang treated CHD by regulating 24 target proteins through 25 therapeutic components
and acting on 21 specific pathways and 4 biological processes.According to the multiple gene chip analysis of GEO2R online
there were up-down-regulated differences in the targets
including 11 up targets and 13 down targets.
Conclusion:
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Xiao Xianxiongtang treats CHD by involving the biological processes through berberine and flavonoid groups of Coptidis Rhizoma
nucleosides and organic acids of
Arum ternatum
Thunb
stigmasterols and flavonoids of
Trichosanthes kirilowii
Maxim
such as gene expression
metabolism and protein metabolism
adjusting the gene expressions of relevant target proteins
regulating gene transcription pathways
such as biological oxidation reaction and lipid and lipoprotein metabolism
insulin-like growth factor binding protein (IGFBPs) of insulin-like growth factor (IGF) transshipment and intake
and the degradation of extracellular matrix signaling pathways.
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