基于网络关键节点分析的中药防治冠心病机制研究
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摘要
该文对冠心病疾病网络、防治冠心病西药作用网络和活血化瘀中药作用网络的交集部分进行分析,计算节点连接度、瓶颈值、中介性等11个网络节点特征参数值,建立了基于支持向量机算法的冠心病-西药交集网络中关键节点特征参数的潜在作用靶标辨识模型,其模型C,γ参数分别为5.14,-1.11,模型对正、负样本的预测正确率达到81.6%,79.2%,对测试集样本的预测敏感性、专一性和准确率分别为81.5%,78.3%,79.6%。并利用模型预测了冠心病-活血化瘀中药交集网络中的潜在作用靶标,共获得180个阳性靶标、42个阴性靶标。本文以钙连蛋白、白介素-1、肿瘤坏死因子等9个阳性靶标为例探讨阐释了中药防治冠心病的作用机制。研究表明网络潜在关键靶标分析方法有助于发掘活血化瘀中药防治冠心病的潜在作用靶点,可为从分子层次和系统层面上揭示中药作用机制提供方法学支持,对中药的作用机制阐释和新药研发具有指导意义。
To analyze the intersections among the western medicine action network for preventing and treating coronary heart disease(CHD),as well as traditional Chinese medicine(TCM) action network for activating blood and dissolving stasis.In this article,11 characteristic parameter values of network nodes,including connectivity,bottleneck,betweenness,were calculated.The target identification model was established based on key node characteristic parameters in the CHD-western medicine intersection network with support vector machine.Its C and γ parameters were 5.14 and-1.11,respectively,with the predicted accuracies for positive and negative samples of 81.6% and 79.2%.The predicted sensitivity,specificity and accuracy of the test set samples were 81.5%,78.3% and 79.6%,respectively.Besides,the model was applied to predict potential action targets of the CHD-activating blood and dissolving stasis TCM intersection network,and 180 positive nodes and 42 negative nodes were obtained.In this article,9 positive nodes,including calnexin,interleukin-1,tumor necrosis factor,were taken as examples to analyze the action mechanism of TCM for preventing and treating CHD.The results showed that the network potential key target analysis method was helpful to explore the potential action targets of activating blood and dissolving stasis TCMs for preventing and treating CHD,methodologically supportive to reveal the action mechanism of TCMs at molecular and systematic levels,and significant in guiding the research and development of new drugs.
To analyze the intersections among the western medicine action network for preventing and treating coronary heart disease(CHD),as well as traditional Chinese medicine(TCM) action network for activating blood and dissolving stasis.In this article,11 characteristic parameter values of network nodes,including connectivity,bottleneck,betweenness,were calculated.The target identification model was established based on key node characteristic parameters in the CHD-western medicine intersection network with support vector machine.Its C and γ parameters were 5.14 and-1.11,respectively,with the predicted accuracies for positive and negative samples of 81.6% and 79.2%.The predicted sensitivity,specificity and accuracy of the test set samples were 81.5%,78.3% and 79.6%,respectively.Besides,the model was applied to predict potential action targets of the CHD-activating blood and dissolving stasis TCM intersection network,and 180 positive nodes and 42 negative nodes were obtained.In this article,9 positive nodes,including calnexin,interleukin-1,tumor necrosis factor,were taken as examples to analyze the action mechanism of TCM for preventing and treating CHD.The results showed that the network potential key target analysis method was helpful to explore the potential action targets of activating blood and dissolving stasis TCMs for preventing and treating CHD,methodologically supportive to reveal the action mechanism of TCMs at molecular and systematic levels,and significant in guiding the research and development of new drugs.
引文
[1]Li S,Zhang Z,Wu L,et al.Understanding ZHENG in tradition-al Chinese medicine in the context of neuro-endocrine-immunenetwork[J].IET Syst Biol,2007,1:51.
[2]Li S,Zhang B,Zhang N B.Network target for screening syner-gistic drug combinations with application to traditional Chinesemedicine[J].BMC Syst Biol,2011,5(S10):1.
[3]李翔,吴磊宏,范晓辉,等.复方丹参方主要活性成分网络药理学研究[J].中国中药杂志,2011,36(21):2911.
[4]黄明峰,张燕玲,任真真,等.网络药理学方法探讨活血化瘀中药治疗冠心病作用机理[J].世界科学技术——中医药现代化,2012,14(5):1969.
[5]Lin C Y,Chin C H,Wu H H,et al.Hubba:hub objects analy-zer-a framework of interactome hubs identification for network bi-ology[J].Nucl Acids Res,2008,36:438.
[6]Vapinkvn.The nature of statistical learning theory[M].NewYork:Springer Verlag,2000.
[7]刘红樱,孙爱军,王时军,等.丹酚酸B通过激活过氧化体增殖物激活型受体γ抑制树突状细胞免疫成熟的作用及其机制[J].中国动脉硬化杂志,2011,19(3):265.
[8]滕菲.缺血心肌细胞凋亡的SIRT1信号转导机制及祛瘀生新法干预研究[D].北京:北京中医药大学,2011.
[9]王战坤,蔡巍,邵乐文,等.细胞因子与冠状动脉狭窄程度的相关性研究[J].中华心血管病杂志,2003,31(8):588.
[10]马国添,李醒三.冠心病与IL-10,IL-4和IFN-γ浓度关系的研究[J].中国现代医学杂志,2004,14(17):37.
[11]田海玲,王国宏.血浆肿瘤坏死因子和白细胞介素与冠心病关系的临床研究[J].全科医疗临床研究,2000,3(6):437.
[12]汤伟.丹参多糖的分离纯化及免疫活性研究[D].广州:南方医科大学,2011.
[13]都丽萍,梅丹,刘昌伟,等.CYP2C9及VKORC1基因多态性对华法林剂量和抗凝效果的影响[J].中国药学杂志,2010,45(21):1628.
[14]谭强,张小勇,李易,等.心肌内注射碱性成纤维细胞生长因子基因对兔缺血心肌血管新生的促进作用[J].中国心血管杂志,2003,8(5):316.
[15]Azfer A,Niu J,Rogers L M,et al.Activation of endoplasmic re-ticulum stress response during the development of ischemic heartdisease[J].Am J Physiol Heart Circ Physiol,2006,291(3):H1411.
[16]孙荣距,闫乐媛,孙建波,等.分化抑制因子1促进血管内皮细胞增殖的机制研究[J].解放军医学杂志,2010,35(4):364.
[17]Wagner S,Chiosea S,Nickerson J A.The spatial targeting andnuclear matrix binding domains of SRm160[J].Proc Natl AcadSci USA,2003,6:3269.
[18]杭兴宜.利用外显子芯片研究缺血/缺氧损伤相关的剪接调控机制[D].北京:中国人民解放军军事医学科学院,2009.
[19]宋光辉.应用基因芯片研究同型半胱氨酸对EVC-3-4细胞基因谱表达的影响[D].郑州:郑州大学,2004.
[20]周四桂,雷小勇,严鹏科,等.缺氧-复氧诱导ECV304细胞与中性粒细胞粘附的分子机制[J].中国动脉粥样硬化杂志,2004,12(4):378.
[21]王婷婷,李柯,魏蕾.血管扩张刺激磷蛋白在细胞骨架调节中的作用[J].生理科学进展,2006,37(1):27.
[22]余小平,曲环,张斌,等.冠心病不稳定斑块凋亡相关基因表达紊乱的机制研究[J].中国老年学杂志,2005,25(12):1493.
[23]庄庭怡,毛静远.冠心病心绞痛与肿瘤坏死因子-α、白介素-1β及白介素-6关系的研究概况[J].中国心血管病研究,2007,5(8):613.
[24]林灼锋.FGF21在动脉粥样硬化发病中的作用及其机制研究[D].广州:暨南大学,2011.
[2]Li S,Zhang B,Zhang N B.Network target for screening syner-gistic drug combinations with application to traditional Chinesemedicine[J].BMC Syst Biol,2011,5(S10):1.
[3]李翔,吴磊宏,范晓辉,等.复方丹参方主要活性成分网络药理学研究[J].中国中药杂志,2011,36(21):2911.
[4]黄明峰,张燕玲,任真真,等.网络药理学方法探讨活血化瘀中药治疗冠心病作用机理[J].世界科学技术——中医药现代化,2012,14(5):1969.
[5]Lin C Y,Chin C H,Wu H H,et al.Hubba:hub objects analy-zer-a framework of interactome hubs identification for network bi-ology[J].Nucl Acids Res,2008,36:438.
[6]Vapinkvn.The nature of statistical learning theory[M].NewYork:Springer Verlag,2000.
[7]刘红樱,孙爱军,王时军,等.丹酚酸B通过激活过氧化体增殖物激活型受体γ抑制树突状细胞免疫成熟的作用及其机制[J].中国动脉硬化杂志,2011,19(3):265.
[8]滕菲.缺血心肌细胞凋亡的SIRT1信号转导机制及祛瘀生新法干预研究[D].北京:北京中医药大学,2011.
[9]王战坤,蔡巍,邵乐文,等.细胞因子与冠状动脉狭窄程度的相关性研究[J].中华心血管病杂志,2003,31(8):588.
[10]马国添,李醒三.冠心病与IL-10,IL-4和IFN-γ浓度关系的研究[J].中国现代医学杂志,2004,14(17):37.
[11]田海玲,王国宏.血浆肿瘤坏死因子和白细胞介素与冠心病关系的临床研究[J].全科医疗临床研究,2000,3(6):437.
[12]汤伟.丹参多糖的分离纯化及免疫活性研究[D].广州:南方医科大学,2011.
[13]都丽萍,梅丹,刘昌伟,等.CYP2C9及VKORC1基因多态性对华法林剂量和抗凝效果的影响[J].中国药学杂志,2010,45(21):1628.
[14]谭强,张小勇,李易,等.心肌内注射碱性成纤维细胞生长因子基因对兔缺血心肌血管新生的促进作用[J].中国心血管杂志,2003,8(5):316.
[15]Azfer A,Niu J,Rogers L M,et al.Activation of endoplasmic re-ticulum stress response during the development of ischemic heartdisease[J].Am J Physiol Heart Circ Physiol,2006,291(3):H1411.
[16]孙荣距,闫乐媛,孙建波,等.分化抑制因子1促进血管内皮细胞增殖的机制研究[J].解放军医学杂志,2010,35(4):364.
[17]Wagner S,Chiosea S,Nickerson J A.The spatial targeting andnuclear matrix binding domains of SRm160[J].Proc Natl AcadSci USA,2003,6:3269.
[18]杭兴宜.利用外显子芯片研究缺血/缺氧损伤相关的剪接调控机制[D].北京:中国人民解放军军事医学科学院,2009.
[19]宋光辉.应用基因芯片研究同型半胱氨酸对EVC-3-4细胞基因谱表达的影响[D].郑州:郑州大学,2004.
[20]周四桂,雷小勇,严鹏科,等.缺氧-复氧诱导ECV304细胞与中性粒细胞粘附的分子机制[J].中国动脉粥样硬化杂志,2004,12(4):378.
[21]王婷婷,李柯,魏蕾.血管扩张刺激磷蛋白在细胞骨架调节中的作用[J].生理科学进展,2006,37(1):27.
[22]余小平,曲环,张斌,等.冠心病不稳定斑块凋亡相关基因表达紊乱的机制研究[J].中国老年学杂志,2005,25(12):1493.
[23]庄庭怡,毛静远.冠心病心绞痛与肿瘤坏死因子-α、白介素-1β及白介素-6关系的研究概况[J].中国心血管病研究,2007,5(8):613.
[24]林灼锋.FGF21在动脉粥样硬化发病中的作用及其机制研究[D].广州:暨南大学,2011.