基于活血化瘀功效的温苦肝、寒苦肝性效关系研究
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摘要
活血化瘀中药是临床上常用的一类功能相同的药物,且多性属寒温,是研究中药药性和功效关系的优良载体。所以为了探讨活血化瘀中药的寒温差异与其功效的内在联系,该文通过数据库检索获取温苦肝、寒苦肝组合的主要有效成分及作用靶点,应用Cytoscape 3. 5. 1平台构建蛋白互作网络,采用Bin GO插件对识别出的功能模块进行功能注释和统计分析,结果表明苦-肝组合主要通过参与细胞周期、脂质代谢、血液循环等生命过程而发挥活血祛瘀的功效;寒性蛋白网络主要通过EDNRA等靶点参与血管收缩、通过PLAU等靶点调节凝血,从而发挥凉血消痈的功效;温性蛋白网络主要通过P2RY12等靶点参与调节血小板活化,从而发挥活血行气、通经止痛的功效。该研究从分子网络水平阐释了苦-肝组合的共性特征和温、寒的特异性特征,为中药的药性与功效的内在联系研究提供了新思路。
Traditional Chinese medicine for promoting blood circulation and removing blood stasis is a kind of drug with cold or warm medicinal properties which is commonly used in clinical practice. It is an excellent carrier for studying the nature-effect relationship of traditional Chinese medicine. Therefore,this study will acquire the main active components and targets based on the drug-based research method. The Cytoscape 3. 5. 1 platform was used to construct the protein interaction network,and the Bin GO plug-in was used to perform functional annotation and statistical analysis on the identified functional modules. The results showed that the bitter-liver protein interaction network mainly participates in cell cycle process,lipid catabolic process,blood circulation to exert the effect of promoting blood circulation and removing blood stasis; the cold protein interaction network mainly participates in vasoconstriction through targets such as EDNRA,regulates blood coagulation through targets such as PLAU,and thus exerts the effect of cooling blood and eliminating phlegm; warm protein interaction network mainly participates in the regulation of platelet activation through targets such as P2 RY12,thereby exerting the effect of promoting blood circulation,relieving pain and relieving pain. This study explains the common characteristics of the bitter-liver combination and the specific characteristics of cold or warm medicinal properties from the molecular network level,which provides a new idea for the intrinsic relationship between the medicinal properties and efficacy of traditional Chinese medicine.
Traditional Chinese medicine for promoting blood circulation and removing blood stasis is a kind of drug with cold or warm medicinal properties which is commonly used in clinical practice. It is an excellent carrier for studying the nature-effect relationship of traditional Chinese medicine. Therefore,this study will acquire the main active components and targets based on the drug-based research method. The Cytoscape 3. 5. 1 platform was used to construct the protein interaction network,and the Bin GO plug-in was used to perform functional annotation and statistical analysis on the identified functional modules. The results showed that the bitter-liver protein interaction network mainly participates in cell cycle process,lipid catabolic process,blood circulation to exert the effect of promoting blood circulation and removing blood stasis; the cold protein interaction network mainly participates in vasoconstriction through targets such as EDNRA,regulates blood coagulation through targets such as PLAU,and thus exerts the effect of cooling blood and eliminating phlegm; warm protein interaction network mainly participates in the regulation of platelet activation through targets such as P2 RY12,thereby exerting the effect of promoting blood circulation,relieving pain and relieving pain. This study explains the common characteristics of the bitter-liver combination and the specific characteristics of cold or warm medicinal properties from the molecular network level,which provides a new idea for the intrinsic relationship between the medicinal properties and efficacy of traditional Chinese medicine.
引文
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[2]陈素红,吕圭源.“性、味结合归经”层面研究中药药性[J].中药药理与临床,2008,24(4):58.
[3]肖斌,王耘,郭维嘉,等.中药药性组合及其与功效的关系研究[J].世界科学技术——中医药现代化,2010,12(6):902.
[4] Ru J,Li P,Wang J,et al. TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform,2014,6(1):13.
[5]魏志成,童东,杨娟,等.基于网络药理学的沙棘总黄酮治疗心肌缺血的作用机制研究[J].中国中药杂志,2017,42(7):1238.
[6]彭涛,周家驹.基于Web的中药化学数据库[J].计算机与应用化学,2004,21(2):181.
[7]刘海波,乔颖欣,刘冰,等.中药化学数据库的数据仓库改造[J].中国药学杂志,2006,41(9):645.
[8] Gaulton A,Bellis L J,Bento A P,et al. ChEMBL:a large-scale bioactivity database for drug discovery[J]. Nucleic Acids Res,2012,40:D1100.
[9] Demchak B,Hull T,Reich M,et al. Cytoscape:the network visualization tool for GenomeSpace workflows[J]. F1000 Res,2014,3:151.
[10] Assenov Y,Ramirez F,Schelhorn S E,et al. Computing topological parameters of biological networks[J]. Bioinformatics,2008,24(2):282.
[11] Hobohm U,Scharf M,Schneider R,et al. Selection of representative protein data sets[J]. Protein Sci,1992,1(3):409.
[12]尚博扬,杨萍,陈丽,等.苦豆子中生物碱成分的网络药理学研究[J].中国中药杂志,2018,43(1):160.
[13]郑世超,任真真,张燕玲,等.基于网络模块分析的降香黄酮类成分抗炎机制研究[J].中国中药杂志,2015,40(8):1565.
[14] Li M,Li D,Tang Y,et al. CytoCluster:acytoscapeplugin for cluster analysis and visualization of biological networks[J]. Int J Mol Sci,2017,18(9):1880.
[15] Li M,Chen J,Wang J,et al. Modifying the DPClus algorithm for identifying protein complexes based on new topological structures[J]. BMC Bioinformatics,2008,9(1):398.
[16]唐羽,李敏.基于Cytoscape的蛋白质网络可视化聚类分析插件[J].生物信息学,2014,12(1):38.
[17] Maere S,Heymans K,Kuiper M. BINGO:a cytoscape plugin to assess overrepresentation of gene ontology categones in biological networks[J]. Bioinformatics,2005,21:3448.
[18]霍晓乾,谷宇,张燕玲.基于网络药理学的大黄利胆片的作用机制研究[J].中国中药杂志,2018,43(13):2770.
[19]王立芳,徐振晔.中药调节细胞周期的研究进展[J].中西医结合学报,2008,6(11):1190.
[20]陈刚,徐晓玉,严鹏科,等.川芎嗪和丹参对小鼠Lewis肺癌生长的抑制作用与抑制血管生成的关系[J].中草药,2004,35(3):296.
[21]汤芷妮,骆云鹏,葛菲,等.活血化瘀抗肿瘤中草药作用机制的研究进展[J].中国药房,2016,27(8):1146.
[22]李燕淑,赵鑫,李麒,等.活血化瘀药物治疗恶性肿瘤作用概述[J].辽宁中医药大学学报,2015,17(5):252.
[23]郜金荣.分子生物学[M].北京:化学工业出版社,2011.
[24]钟赣生.中药学[M].北京:中国中医药出版社,2016:21.
[25]任雪梅,杨光福.中药药性理论之四气研究进展[J].医学研究与教育,2009,26(5):90.
[26]房雅楠,隋汝波.EDNRA和EDNRB基因单核苷酸位点多态性与缺血性脑卒中的相关性[J].中国老年学杂志,2016,36(18):4446.
[27]周志化. Plat、Plau激活内皮细胞膜上纤溶酶促血栓消退的研究[D].昆明:昆明医科大学,2014.
[28]张亚楠,崔炜.P2RY12(P2Y12)基因多态性与氯吡格雷抵抗的关系[J].临床荟萃,2009,24(8):731.
[29]王文祥,熊晓滨,毛卫红.姜黄素对高脂血症兔血液流变学、血小板聚集、抗氧化以及纤溶系统的影响[J].中国现代应用药学,2013,30(6):598.
[30]刘剑刚,张大武,李婕,等.丹参、红花水溶性组分及配伍对大鼠心肌缺血/再灌注损伤作用的实验研究[J].中国中药杂志,2011,36(2):189.
[31] Dupuis J,Langenberg C,Prokopenko I,et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type2 diabetes risk[J]. Nat Genet,2010,42(2):105.