常用补气、活血、破血药对治疗冠心病的分子机制预测
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摘要
目的：
1.探索冠心病(coronary heart disease,CHD)常见证候分布规律及中药配伍应用规律；
2.预测常用补气、活血、破血药对治疗CHD分子机制。
方法：
在中国生物医学文献数据库中收集治疗CHD文献数据,采用基于敏感关键词频数统计的数据分层算法,文本挖掘冠心病中医证候、中药规律,这些规律通过一维频次表及二维的网络图进行展示,得出CHD常见证候及其相应治疗用药。以最高频次证候关联性强的中药药对及人工分析方法补充纳入适当的中药为研究对象,利用PubChem查找这些药物的相应人类靶蛋白,同时从PubMed基因库中检索到CHD基因,把这些药物靶蛋白及CHD基因分别导入到IPA分析平台(Ingenuity Pathways Analysis,IPA)得到相应的网络、通路、分子等,通过对比分析药物与CHD间的网络、通路、分子等,探索、预测药对治疗CHD的分子机制。
结果：
1.文本挖掘结果显示CHD证型以气虚血瘀型为主,中药以黄芪与人参、丹参与三七彼此间关联性好,也是治疗气虚血瘀型的常见补气、活血药对。本研究选取这两个药对及用人工分析方法纳入破血药对三棱与莪术,探索这些药物治疗CHD的分子机制。
2.生物信息学分析发现补气、活血、破血药对与CHD部分网络间有共同分子交联,共同交联的药物靶分子有HIF1A、ESR1、CYP3A4、PPARD、PLA2G7、OPRM1、MMP2、 ALB、ESR2、CYP2C19、PPARG、PPARA共12个。
3.补气、活血、破血药对与CHD生物学通路相关性有一定的规律性：①补气、活血药对与心血管信号通路相关性好；②补气药对与细胞因子通路及细胞生长,分化与发育信号通路相关性好；③活血药对与核受体信号通路相关性好；④活血、破血药对与代谢通路相关性好；⑤三个药对与细胞内第二信使信号通路相关性各有不同。
4.补气、活血、破血药对与CHD部分生物学通路间有共同分子交联,共同交联的药物靶分子有HIF1A、ESR1、CYP3A4、PPARD、PLA2G7、OPRM1、MMP2、ALB、ESR2、CYP2C19、 PPARG、PPARA共12个。补气、活血、破血药对与CHD网络、通路共同交联的靶分子中,①三个药对共有的靶分子有HIF1A、ESR1、CYP3A4;②补气、活血药对共有的靶分子有PPARD、PLA2G7;③活血、破血药对共有的靶分子有OPRM1;④补气药对独有的靶分子有MMP2、ALB;⑤活血药对独有的靶分子有ESR2、CYP2C19、PPARG、PPARA。
结论：
1.文本挖掘结果显示气虚血瘀证是CHD最主要、最常见的证型,反映了CHD的中医基本病机特点；丹参配三七、人参配黄芪是中医治疗CHD常用的补气、活血药对。文本挖掘结果反映了CHD中医临床诊治实际。
2.补气、活血、破血药对与CHD相关生物学网络、通路间有共同交联的药物靶分子有HIF1A、ESR1、CYP3A4等12个。三个药对通过与CHD共同交联的药物靶分子,调控CHD的相关通路、网络可能是三个药对治疗CHD的分子机制,同时也体现了这种调控是多靶点、多途径的。
3.三个药对与CHD生物学通路相关性有一定的规律性,这些规律性,反应了三个药对影响CHD的特点。三个药对影响CHD有共同之处,如三者均可能通过其共有的靶分子HIF1A调控Hypoxia Signaling in Cardiovascular System、HIF1α Signaling、 VEGF Signaling等生物学通路；三者也有不同之处,如活血、破血药对可能通过其共有的靶基因OPRM1调控G-Protein Coupled Receptor Signaling通路,补气药对可能通过其独有的靶基因MMP2调控HIF1α Signaling与IL-8Signaling通路。这些异、同之处,反映了三者单独或者联合治疗CHD的分子机制,为三者单独或者联合治疗CHD提供了分子机制理论依据,也为三者基于中医理论功效主治上的异、同提供了分子理论思路。
4.文本挖掘技术结合生物信息学分析技术是探索、预测中药治疗疾病分子网络机制的有效方法。
Objective
1. To explore the regularities of common syndrome and Chinese herbal medicines (CHMs) on CHD.
2. To forecast the molecular mechanisms of CHD treatment by the common drug pairs of invigorating qi, promoting blood circulation and blood-breaking drugs.
Methods
The data set on CHD was downloaded from Chinese BioMedical literature database. The regularities of traditional Chinese medicine (TCM) syndrome and CHMs on CHD were mined out by data slicing algorithm based on algorithms of discrete derivative, and key words directed text mining. The results were demonstrated with tables and networks, and then the main TCM syndrome of CHD and its corresponding CHMs could be obtained. CHMs which were strongly associated with the top TCM syndrome were selected for the study and some CHMs were recruited by manual analysis method. Through retrieved PubChem, human target proteins of the CHMs were obtained. Meanwhile, CHD genes were got through PubMed "Gene" database. Then the proteins and genes were imported into IPA platform respectively to get the corresponding networks, pathways and molecules etc. by compared and analyzed these networks, pathways, molecules etc., the molecular mechanisms for the treatment of CHD could be explored and forecasted.
Results
1. Qi deficiency and blood stasis was the main TCM syndrome of CHD found with text mining. CHMs such as astragalus, ginseng, salvia miltiorrhiza and notoginseng were intimately associated with each other and they were also often used as the pairs of invigorating qi and promoting blood circulation for treatment of CHD with qi deficiency and blood stasis syndrome. These four CHMs plus blood-breaking drugs rhizoma sparganii and rhizoma curcumae by manual analysis method were seclected for this study to explored the molecular mechanisms for the treatment of CHD.
2. Altogether there were12common molecules between CHD gene networks and three drug pairs networks found with bioinformatics analysis. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG,OPRM1were included.
3. There were certain regularities between CHD pathways and three drug pairs pathways discovered. For example, drug pairs of invigorating qi and promoting blood circulation had a high correlation with Cardiovascular Singnaling; while invigorating qi drug pairs had a high correlation with Cytokine Singnaling and Cellular Growth, Proliferation and Development; and drug pairs of promoting blood circulation had a high correlation with Nuclear Receptor Signaling; drug pairs of promoting blood circulation and blood-breaking drugs had a high correlation with Metabolic Pathway.
4. Altogether there were12common molecules between CHD gene pathways and three drug pairs pathways found. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG, OPRM1were included. Among these common targets of networks and pathways, HIF1A, ESR1and CYP3A4were the common targets of three drug pairs; PPARD and PLA2G7were the common targets of drug pairs of invigorating qi and promoting blood circulation; OPRM1was the common targests of promoting blood circulation and blood-breaking drug pairs; MMP2and ALB were the targets of invigorating qi drugs pairs; ESR2, CYP2C19, PPARG and PPARA were the targets of promoting blood circulation drugs pairs.
Conelusions
1. Qi deficiency and blood stasis was the main TCM syndrome of CHD which reflected the basic pathogenesis of CHD in TCM. Astragalus, in combination with ginseng, salvia miltiorrhiza and notoginseng, were used as the common drug pairs for treatment of CHD in TCM. The results of text mining reflected the clinical diagnosis and treatment of CHD in TCM.
2. Altogether there were12common targets such as HIFIA、ESR1、CYP3A4in the biological networks and pathways between CHD gene and three drug pairs. Three drug pairs through these targets regulate CHD pathways, networks may be the mechanisms of the drug pairs for the treatment of CHD, which also reflect the drug pairs may regulate CHD through multi-targets and multi-pathways.
3. There were certain regularities between CHD pathways and three drug pairs pathways, and these regularities reflect characteristics of the three drug pairs on the impact of CHD. Three drug pairs had something in common for affecting CHD. For example,three of them could regulate the pathways such as Hypoxia Signaling in Cardiovascular System, HIF1α Signaling, VEGF Signaling through HIF1A. However, three of them had something different, for example, salvia miltiorrhiza and notoginseng, rhizoma sparganii and rhizoma curcumae could regulate G-Protein Coupled Receptor Signaling through OPRM1, and astragalus and ginseng could regulate the pathways such as HIF1α Signaling and IL-8Signaling through MMP2. The similarities and differences between the durg pairs reflect the molecular mechanisms of CHD treatment by the durg pairs alone or together, which provide the theoretical basis of molecular mechanisms for CHD treatment by the durg pairs alone or together, and also provide the molecular theoretical thinking for similarities and differences of efficacy and indications based on the theory of traditional Chinese medicine between the durg pairs.
4. It is an effective approach to explore and forecast the molecular network mechanisms of disease in TCM through combined text mining technology with bioinformatics analysis.
1.探索冠心病(coronary heart disease,CHD)常见证候分布规律及中药配伍应用规律；
2.预测常用补气、活血、破血药对治疗CHD分子机制。
方法：
在中国生物医学文献数据库中收集治疗CHD文献数据,采用基于敏感关键词频数统计的数据分层算法,文本挖掘冠心病中医证候、中药规律,这些规律通过一维频次表及二维的网络图进行展示,得出CHD常见证候及其相应治疗用药。以最高频次证候关联性强的中药药对及人工分析方法补充纳入适当的中药为研究对象,利用PubChem查找这些药物的相应人类靶蛋白,同时从PubMed基因库中检索到CHD基因,把这些药物靶蛋白及CHD基因分别导入到IPA分析平台(Ingenuity Pathways Analysis,IPA)得到相应的网络、通路、分子等,通过对比分析药物与CHD间的网络、通路、分子等,探索、预测药对治疗CHD的分子机制。
结果：
1.文本挖掘结果显示CHD证型以气虚血瘀型为主,中药以黄芪与人参、丹参与三七彼此间关联性好,也是治疗气虚血瘀型的常见补气、活血药对。本研究选取这两个药对及用人工分析方法纳入破血药对三棱与莪术,探索这些药物治疗CHD的分子机制。
2.生物信息学分析发现补气、活血、破血药对与CHD部分网络间有共同分子交联,共同交联的药物靶分子有HIF1A、ESR1、CYP3A4、PPARD、PLA2G7、OPRM1、MMP2、 ALB、ESR2、CYP2C19、PPARG、PPARA共12个。
3.补气、活血、破血药对与CHD生物学通路相关性有一定的规律性：①补气、活血药对与心血管信号通路相关性好；②补气药对与细胞因子通路及细胞生长,分化与发育信号通路相关性好；③活血药对与核受体信号通路相关性好；④活血、破血药对与代谢通路相关性好；⑤三个药对与细胞内第二信使信号通路相关性各有不同。
4.补气、活血、破血药对与CHD部分生物学通路间有共同分子交联,共同交联的药物靶分子有HIF1A、ESR1、CYP3A4、PPARD、PLA2G7、OPRM1、MMP2、ALB、ESR2、CYP2C19、 PPARG、PPARA共12个。补气、活血、破血药对与CHD网络、通路共同交联的靶分子中,①三个药对共有的靶分子有HIF1A、ESR1、CYP3A4;②补气、活血药对共有的靶分子有PPARD、PLA2G7;③活血、破血药对共有的靶分子有OPRM1;④补气药对独有的靶分子有MMP2、ALB;⑤活血药对独有的靶分子有ESR2、CYP2C19、PPARG、PPARA。
结论：
1.文本挖掘结果显示气虚血瘀证是CHD最主要、最常见的证型,反映了CHD的中医基本病机特点；丹参配三七、人参配黄芪是中医治疗CHD常用的补气、活血药对。文本挖掘结果反映了CHD中医临床诊治实际。
2.补气、活血、破血药对与CHD相关生物学网络、通路间有共同交联的药物靶分子有HIF1A、ESR1、CYP3A4等12个。三个药对通过与CHD共同交联的药物靶分子,调控CHD的相关通路、网络可能是三个药对治疗CHD的分子机制,同时也体现了这种调控是多靶点、多途径的。
3.三个药对与CHD生物学通路相关性有一定的规律性,这些规律性,反应了三个药对影响CHD的特点。三个药对影响CHD有共同之处,如三者均可能通过其共有的靶分子HIF1A调控Hypoxia Signaling in Cardiovascular System、HIF1α Signaling、 VEGF Signaling等生物学通路；三者也有不同之处,如活血、破血药对可能通过其共有的靶基因OPRM1调控G-Protein Coupled Receptor Signaling通路,补气药对可能通过其独有的靶基因MMP2调控HIF1α Signaling与IL-8Signaling通路。这些异、同之处,反映了三者单独或者联合治疗CHD的分子机制,为三者单独或者联合治疗CHD提供了分子机制理论依据,也为三者基于中医理论功效主治上的异、同提供了分子理论思路。
4.文本挖掘技术结合生物信息学分析技术是探索、预测中药治疗疾病分子网络机制的有效方法。
Objective
1. To explore the regularities of common syndrome and Chinese herbal medicines (CHMs) on CHD.
2. To forecast the molecular mechanisms of CHD treatment by the common drug pairs of invigorating qi, promoting blood circulation and blood-breaking drugs.
Methods
The data set on CHD was downloaded from Chinese BioMedical literature database. The regularities of traditional Chinese medicine (TCM) syndrome and CHMs on CHD were mined out by data slicing algorithm based on algorithms of discrete derivative, and key words directed text mining. The results were demonstrated with tables and networks, and then the main TCM syndrome of CHD and its corresponding CHMs could be obtained. CHMs which were strongly associated with the top TCM syndrome were selected for the study and some CHMs were recruited by manual analysis method. Through retrieved PubChem, human target proteins of the CHMs were obtained. Meanwhile, CHD genes were got through PubMed "Gene" database. Then the proteins and genes were imported into IPA platform respectively to get the corresponding networks, pathways and molecules etc. by compared and analyzed these networks, pathways, molecules etc., the molecular mechanisms for the treatment of CHD could be explored and forecasted.
Results
1. Qi deficiency and blood stasis was the main TCM syndrome of CHD found with text mining. CHMs such as astragalus, ginseng, salvia miltiorrhiza and notoginseng were intimately associated with each other and they were also often used as the pairs of invigorating qi and promoting blood circulation for treatment of CHD with qi deficiency and blood stasis syndrome. These four CHMs plus blood-breaking drugs rhizoma sparganii and rhizoma curcumae by manual analysis method were seclected for this study to explored the molecular mechanisms for the treatment of CHD.
2. Altogether there were12common molecules between CHD gene networks and three drug pairs networks found with bioinformatics analysis. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG,OPRM1were included.
3. There were certain regularities between CHD pathways and three drug pairs pathways discovered. For example, drug pairs of invigorating qi and promoting blood circulation had a high correlation with Cardiovascular Singnaling; while invigorating qi drug pairs had a high correlation with Cytokine Singnaling and Cellular Growth, Proliferation and Development; and drug pairs of promoting blood circulation had a high correlation with Nuclear Receptor Signaling; drug pairs of promoting blood circulation and blood-breaking drugs had a high correlation with Metabolic Pathway.
4. Altogether there were12common molecules between CHD gene pathways and three drug pairs pathways found. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG, OPRM1were included. Among these common targets of networks and pathways, HIF1A, ESR1and CYP3A4were the common targets of three drug pairs; PPARD and PLA2G7were the common targets of drug pairs of invigorating qi and promoting blood circulation; OPRM1was the common targests of promoting blood circulation and blood-breaking drug pairs; MMP2and ALB were the targets of invigorating qi drugs pairs; ESR2, CYP2C19, PPARG and PPARA were the targets of promoting blood circulation drugs pairs.
Conelusions
1. Qi deficiency and blood stasis was the main TCM syndrome of CHD which reflected the basic pathogenesis of CHD in TCM. Astragalus, in combination with ginseng, salvia miltiorrhiza and notoginseng, were used as the common drug pairs for treatment of CHD in TCM. The results of text mining reflected the clinical diagnosis and treatment of CHD in TCM.
2. Altogether there were12common targets such as HIFIA、ESR1、CYP3A4in the biological networks and pathways between CHD gene and three drug pairs. Three drug pairs through these targets regulate CHD pathways, networks may be the mechanisms of the drug pairs for the treatment of CHD, which also reflect the drug pairs may regulate CHD through multi-targets and multi-pathways.
3. There were certain regularities between CHD pathways and three drug pairs pathways, and these regularities reflect characteristics of the three drug pairs on the impact of CHD. Three drug pairs had something in common for affecting CHD. For example,three of them could regulate the pathways such as Hypoxia Signaling in Cardiovascular System, HIF1α Signaling, VEGF Signaling through HIF1A. However, three of them had something different, for example, salvia miltiorrhiza and notoginseng, rhizoma sparganii and rhizoma curcumae could regulate G-Protein Coupled Receptor Signaling through OPRM1, and astragalus and ginseng could regulate the pathways such as HIF1α Signaling and IL-8Signaling through MMP2. The similarities and differences between the durg pairs reflect the molecular mechanisms of CHD treatment by the durg pairs alone or together, which provide the theoretical basis of molecular mechanisms for CHD treatment by the durg pairs alone or together, and also provide the molecular theoretical thinking for similarities and differences of efficacy and indications based on the theory of traditional Chinese medicine between the durg pairs.
4. It is an effective approach to explore and forecast the molecular network mechanisms of disease in TCM through combined text mining technology with bioinformatics analysis.
引文
[1]陆再英,钟南山.内科学[M].北京：人民卫生出版社,2008,267-302.
[2]吴临爱.冠心病临床流行病学调查及干预对策[J].山西医药杂志(下半月刊),2012,41(5)：452-454.
[3]滕龙,洪芳,何建成.冠心病中医证候微观诊断指标的研究进展[J].时珍国医国药,2012,23(12)：3119-3121.
[4]王少青,刘朋,刘颖,等.复方丹参滴丸抗动脉粥样硬化研究进展[J].中国新药杂志,2012,21(15)：1765-1768.
[5]周忠冉,唐海沁,李结华,等.通心络胶囊治疗冠心病疗效及安全性的系统评价[J].中国循证医学杂志,2011,11(9)：1078-1083.
[6]姚惠,郑培奋,陈建明,等.丹参川芎汤辨证治疗老年气阴两虚血瘀型冠心病的临床疗效分析[J].浙江中医药大学学报,2012,36(12)：1312-1314.
[7]陈会君,周亚滨,王岩.养心汤治疗冠心病不稳定型心绞痛经验撷菁[J].辽宁中医药大学学报,2012,14(12)：60-61.
[8]薛为民,陆玉昌.文本挖掘技术研究[J].北京联合大学学报(自然科学版),2005,19(4)：59-63.
[9]Luscombe N. M., Greenbaum D., Gerstein M. What is bio informatics? A proposed definition and overview of the field[J]. Methods Inf Med,2001,40 (4):346-358.
[10]王非.中药现代化的EXPRESSWAY——利用生物信息学推动中药现代化[J].中国处方药,2002,(7)：44-46.
[11]Zheng G., Jiang M., He X., et al. Discrete derivative:a data slicing algorithm for exploration of sharing biological networks between rheumatoid arthritis and coronary heart disease[J]. BioData Min,2011,418.
[12]宋燕青,徐向阳,孙仁弟.注射用丹参多酚酸盐的临床应用概述[J].药物流行病学杂志,2012,21(8)：404-407.
[13]刘芳,戴小华.益气活血中药改善冠心病患者血管内皮功能临床研究进展[J].中医药临床杂志,2012,1(24)：
[14]李伟.丹参注射液治疗冠心病心绞痛的疗效分析[J].中国当代医药,2011,18(31)：72,74.
[15]黄海波,李彦会,王文星,等.三七心血通胶囊治疗痰阻心脉型冠心病心绞痛临床观察[J].河北中医,2012,34(7)：987-988.
[16]郭洪涛,郑光,赵静,等.基于文本挖掘分析甲型H1N1流感的中医药治疗特色[J].世界科学技术(中医药现代化),2011,13(5)：772-776.
[17]吴焕林,王侠,李晓庆.126例急性心肌梗死病人证候特点的回顾性分析[J].辽宁中医杂志,2010,37(9)：1749-1750.
[18]郑国华,熊尚全,周锟,等.福州地区507例汉族冠心病患者中医证型分布规律研究[J].中国中西医结合杂志,2011,31(6)：756-759.
[19]葛永彬,毛静远.7512例冠心病中医证型分布规律分析[J].山东中医杂志,2011,30(4)：227-229.
[20]毛静远,牛子长,张伯礼.近40年冠心病中医证候特征研究文献分析[J].中医杂志,2011,52(11)：958-961.
[21]刘陶世,黄耀洲.丹参成分、制剂和质量控制研究概况[J].南京中医药大学学报,1998,14(4)：66-67.
[22]林峰,石杰.丹参活性成分的药效药理作用[J].医学信息(上旬刊),2011,24(6)：3813-3814.
[23]高传长,邹书兵.丹参及其主要成分在冠心病及胰腺炎等疾病中的治病机制[J].中国中西医结合杂志,2010,30(11)：1222-1227.
[24]张喜平,齐丽丽,刘达人.三七及其有效成分的药理作用研究现状[J].医学研究杂志,2007,36(4)：96-98.
[25]蔡广,叶常青,许祯,等.三七总甙注射液治疗冠心病的疗效[J].心脏杂志,2006,18(5)：562-564+567.
[26]邱勇波,刘锦,武飞.黄芪化学成分及药理作用研究进展[J].中国疗养医学,2011,20(5)：435-436.
[27]张蔷,高文远,满淑丽.黄芪中有效成分药理活性的研究进展[J].中国中药杂志,2012,37(21)：3203-3207.
[28]郭秀丽,高淑莲.人参化学成分和药理研究进展[J].中医临床研究,2012,4(14)：26-27.
[29]王悦虹,娄大伟,于晓洋,等.人参的药理学作用研究进展[J].吉林化工学院学报,2010,27(2)：38-41.
[30]张念志,韩明向,周宜轩,等.人参注射液对冠心病心绞痛心气虚证作用的临床研究[J].中国中医急症,2000,9(4)：141-136.
[31]丘瑞香,金明华,吴国珍.人参对老年冠心病肾虚患者性激素双向调节的研究[J].中医杂志,1997,38(11)：672-674.
[32]赵熙灼,梁炳圻,洪行球,等.人参芦皂甙治疗冠心病的临床研究——294例报告[J].中药药理与临床,1991,7(5)：34-37.
[33]王薇娜,赵良平,王丽,等.人参皂甙Rb_1对大鼠急性心肌梗死后左室重构的影响[J].中国微循环,2006,10(4)：256-258.
[34]谢海波,莫新民,罗尧岳.活血药、破血药对动脉粥样硬化大鼠血脂、血液流变学的影响[J].湖南中医药大学学报,2010,30.(3)：20-22.
[35]钱伟,赵福海,史大卓.莪术及其提取物的心血管药理研究进展[J].中国中西医结合杂志,2012,32(4)：575-576.
[36]和岚,张秀梅,毛腾敏.三棱、丹参对血液流变学影响的比较研究[J].山东中医药大学学报,2007,31(5)：434-435.
[37]李建民.三棱莪术汤治疗冠心病稳定型心绞痛临床观察[J].天津中医药,2007,24(6)：470-471.
[38]许忠能.生物信息学发展与中草药研究[J].中草药,2003,34(6)：481-486.
[39]孙排正.镍离子细胞毒性差异表达基因生物信息学分析.硕士论文.东南大学,84-90.2008,
[40]Greer S. N., Metcalf J. L., Wang Y., et al. The updated biology of hypoxia-inducible factor[J]. EMBO J,2012,31 (11):2448-2460.
[41]Wang G. L., Jiang B. H., Rue E. A., et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular 02 tension[J]. Proc Natl Acad Sci U S A,1995,92 (12):5510-5514.
[42]Wang G. L.,Semenza G. L. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia[J]. J Biol Chem,1993,268 (29): 21513-21518.
[43]Dayan F., Roux D., Brahimi-Horn M. C., et al. The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-lalpha[J]. Cancer Res,2006,66 (7):3688-3698.
[44]Jiang B. H., Zheng J. Z., Leung S. W., et al. Transactivation and inhibitory domains of hypoxia-inducible factor lalpha. Modulation of transcriptional activity by oxygen tension[J]. J Biol Chem,1997,272 (31):19253-19260.
[45]Huang L. E., Gu J., Schau M., et al. Regulation of hypoxia-inducible factor lalpha is mediated by an 02-dependent degradation domain via the ubiquitin-proteasome pathway [J]. Proc Natl Acad Sci U S A,1998,95 (14):7987-7992.
[46]Poon E., Harris A. L., Ashcroft M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer[J]. Expert Rev Mol Med,2009,11 e26.
[47]Semenza G. L. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J]. Oncogene,2010,29 (5):625-634.
[48]Ivan M., Kondo K., Yang H., et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation:implications for 02 sensing[J]. Science,2001,292 (5516): 464-468.
[49]Jaakkola P., Mole D. R., Tian Y. M., et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by 02-regulated prolyl hydroxylation[J]. Science, 2001,292 (5516):468-472.
[50]Masson N., Willam C., Maxwell P. H., et al. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation[J]. EMBO J,2001,20 (18):5197-5206.
[51]Ahluwalia A..Tarnawski A. S. Critical role of hypoxia sensor--HIF-lalpha in VEGF gene activation. Implications for angiogenesis and tissue injury healing[J]. Curr Med Chem,2012,19 (1):90-97.
[52]Date T., Mochizuki S., Belanger A. J., et al. Expression of constitutively stable hybrid hypoxia-inducible factor-lalpha protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury[J]. Am J Physiol Cell Physiol,2005,288 (2): C314-320.
[53]Dendorfer A., Heidbreder M., Hellwig-Burgel T., et al. Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals[J]. Free Radic Biol Med,2005,38 (1):117-124.
[54]Ockaili R., Natarajan R., Salloum F., et al. HIF-1 activation attenuates postischemic myocardial injury:role for heme oxygenase-1 in modulating microvascular chemokine generation[J]. Am J Physiol Heart Circ Physiol,2005,289 (2):H542-548.
[55]Belaidi E., Beguin P. C., Levy P., et al. Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium results in loss of myocardial hypoxic preconditioning in the rat[J]. Am J Physiol Heart Circ Physiol,2008,294 (2):H901-908.
[56]Natarajan R., Salloum F. N., Fisher B. J., et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury [J]. J Cardiovasc Pharmacol,2008,51 (2):178-187.
[57]Tekin D., Dursun A. D., Xi L. Hypoxia inducible factor 1 (HIF-1) and cardioprotection[J]. Acta Pharmacol Sin,2010,31 (9):1085-1094.
[58]Ong S. G., Hausenloy D. J. Hypoxia-inducible factor as a therapeutic target for cardioprotection[J]. Pharmacol Ther,2012,136 (1):69-81.
[59]Blagosklonny M. V., An W. G., Romanova L. Y., et al. p53 inhibits hypoxia-inducible factor-stimulated transcription[J]. J Biol Chem,1998,273 (20):11995-11998.
[60]Suzuki H., Tomida A., Tsuruo T. Dephosphorylated hypoxia-inducible factor lalpha as a mediator of p53-dependent apoptosis during hypoxia[J]. Oncogene,2001,20 (41): 5779-5788.
[61]Semenza G. L. Regulation of oxygen homeostasis by hypoxia-inducible factor 1[J]. Physiology (Bethesda),2009,24 97-106.
[62]Loor G., Schumacker P. T. Role of hypoxia-inducible factor in cell survival during myocardial ischemia-reperfusion[J]. Cell Death Differ,2008,15 (4):686-690.
[63]Zachary I., Mathur A., Yla-Herttuala S., et al. Vascular protection:A novel nonangiogenic cardiovascular role for vascular endothelial growth factor[J]. Arterioscler Thromb Vasc Biol,2000,20 (6):1512-1520.
[64]Inoue M., Itoh H., Ueda M., et al. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions:possible pathophysiological significance of VEGF in progression of atherosclerosis[J]. Circulation,1998,98 (20): 2108-2116.
[65]Banai S., Jaklitsch M. T., Shou M., et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs[J]. Circulation,1994,89 (5):2183-2189.
[66]Oloumi A., Syam S., Dedhar S. Modulation of Wnt3a-mediated nuclear beta-catenin accumulation and activation by integrin-linked kinase in mammalian cells[J]. Oncogene, 2006,25 (59):7747-7757.
[67]Cho H. J., Youn S. W., Cheon S. I., et al. Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase[J]. Arterioscler Thromb Vasc Biol,2005,25 (6):1154-1160.
[68]Traister A., Aafaqi S., Masse S., et al. ILK induces cardiomyogenesis in the human heart[J]. PLoS One,2012,7 (5):e37802.
[69]Tseng W. P., Yang S. N., Lai C. H., et al. Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts[J]. J Cell Physiol,2010,223 (3):810-818.
[70]Leyme A., Bourd-Boittin K., Bonnier D., et al. Identification of ILK as a new partner of the ADAM12 disintegrin and metalloprotease in cell adhesion and survival [J]. Mol Biol Cell,2012,23 (17):3461-3472.
[71]Wani A. A., Jafarnejad S. M., Zhou J., et al. Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kappaB/interleukin-6 signaling pathway[J]. Oncogene,2011,30 (24):2778-2788.
[72]Tan C., Cruet-Hennequart S., Troussard A., et al. Regulation of tumor angiogenesis by integrin-linked kinase (ILK)[J]. Cancer Cell,2004,5 (1):79-90.
[73]Ding L., Dong L., Chen X., et al. Increased expression of integrin-linked kinase attenuates left ventricular remodeling and improves cardiac function after myocardial infarction[J]. Circulation,2009,120 (9):764-773.
[74]Bendig G., Grimmler M., Huttner I. G., et al. Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart[J]. Genes Dev,2006,20 (17):2361-2372.
[75]Moeller L. C., Broecker-Preuss M. Transcriptional regulation by nonclassical action of thyroid hormone[J]. Thyroid Res,2011,4 Suppl 1 S6.
[76]Moeller L. C., Cao X., Dumitrescu A. M., et al. Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway[J]. Nucl Recept Signal,2006,4 e020.
[77]薛增明,马长生.甲状腺激素降低与心血管疾病[J].中国实用内科杂志,2012,32(10)：804-806.
[78]Singh S., Duggal J., Molnar J., et al. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality:a meta-analysis[J]. Int J Cardiol,2008,125 (1):41-48.
[79]Coceani M., Iervasi G., Pingitore A., et al. Thyroid hormone and coronary artery disease:from clinical correlations to prognostic implications[J]. Clin Cardiol,2009, 32 (7):380-385.
[80]Rodondi N., Aujesky D., Vittinghoff E., et al. Subclinical hypothyroidism and the risk of coronary heart disease:a meta-analysis[J]. Am J Med,2006,119 (7):541-551.
[81]Kong H. L., Wang J. P., Li Z. Q., et al. Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo[J]. Acta Pharmacol Sin,2009,30 (4):396-403.
[82]Leung K. W., Ng H. M., Tang M. K., et al. Ginsenoside-Rgl mediates a hypoxia-independent upregulation of hypoxia-inducible factor-lalpha to promote angiogenesis[J]. Angiogenesis,2011,14 (4):515-522.
[83]Shen K., Ji L., Gong C., et al. Notoginsenoside Ftl promotes angiogenesis via HIF-lalpha mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways[J]. Biochem Pharmacol,2012,84 (6):784-792.
[84]Xu W., Yang J.,Wu L. M. Cardioprotective effects of tanshinone IIA on myocardial ischemia injury in rats[J]. Pharmazie,2009,64 (5):332-336.
[85]Zhang L., Liu Q., Lu L., et al. Astragaloside IV stimulates angiogenesis and increases hypoxia-inducible factor-lalpha accumulation via phosphatidylinositol 3-kinase/Akt pathway[J]. J Pharmacol Exp Ther,2011,338 (2):485-491.
[86]杜雪君,雷燕,杨静.人参三七组方对急性心肌梗死大鼠缺血心肌血管内皮生长因子受体2和缺氧诱导因子1 α表达的影响[J].中西医结合学报,2010,8(6)：548-553.
[87]Deschamps A. M., Murphy E., Sun J. Estrogen receptor activation and cardioprotection in ischemia reperfusion injury[J]. Trends Cardiovasc Med,2010,20 (3):73-78.
[88]Enmark E., Gustaf sson J. A. Oestrogen receptors-an overview[J]. J Intern Med,1999, 246 (2):133-138.
[89]Shao W., Brown M. Advances in estrogen receptor biology:prospects for improvements in targeted breast cancer therapy[J]. Breast Cancer Res,2004,6 (1):39-52.
[90]Pike A. C. Lessons learnt from structural studies of the oestrogen receptor [J]. Best Pract Res Clin Endocrinol Metab,2006,20 (1):1-14.
[91]Shang Y., Hu X., DiRenzo J., et al. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription[J]. Cell,2000,103 (6):843-852.
[92]Rao B. R. Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs[J]. J Steroid Biochem Mol Biol,1998,65 (1-6):3-41.
[93]Ignar-Trowbridge D. M., Nelson K. G., Bidwell M. C., et al. Coupling of dual signaling pathways:epidermal growth factor action involves the estrogen receptor[J]. Proc Natl Acad Sci U S A,1992,89 (10):4658-4662.
[94]Kato S. Estrogen receptor-mediated cross-talk with growth factor signaling pathways[J]. Breast Cancer,2001,8 (1):3-9.
[95]Lee H., Bai W. Regulation of estrogen receptor nuclear export by ligand-induced and p38-mediated receptor phosphorylation[J]. Mol Cell Biol,2002,22 (16):5835-5845.
[96]Joel P. B., Smith J., Sturgill T. W., et al. pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167[J]. Mol Cell Biol, 1998,18 (4):1978-1984.
[97]Razandi M., Pedram A., Greene G. L., et al. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript:studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells[J]. Mol Endocrinol,1999,13 (2):307-319.
[98]Toran-Allerand C. D. Novel sites and mechanisms of oestrogen action in the brain[J]. Novartis Found Symp,2000,230 56-69; discussion 69-73.
[99]Kousteni S., Bellido T., Plotkin L. I., et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors:dissociation from transcriptional activity[J]. Cell,2001,104 (5):719-730.
[100]Yang X. P.,Reckelhoff J. F. Estrogen, hormonal replacement therapy and cardiovascular disease[J]. Curr Opin Nephrol Hypertens,2011,20 (2):133-138.
[101]Mendelsohn M. E.,Karas R. H. The protective effects of estrogen on the cardiovascular system[J]. N Engl J Med,1999,340 (23):1801-1811.
[102]Bakir S., Mori T., Durand J., et al. Estrogen-induced vasoprotection is estrogen receptor dependent:evidence from the balloon-injured rat carotid artery model[J]. Circulation,2000,101 (20):2342-2344.
[103]Chen Z., Yuhanna I. S., Galcheva-Gargova Z., et al. Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen[J]. J Clin Invest,1999,103 (3):401-406.
[104]Dubey R. K., Jackson E. K., Gillespie D. G., et al. Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity[J]. Arterioscler Thromb Vasc Biol,2000,20 (4):964-972.
[105]Hodges Y. K., Tung L., Yan X. D., et al. Estrogen receptors alpha and beta:prevalence of estrogen receptor beta mRNA in human vascular smooth muscle and transcriptional effects[J]. Circulation,2000,101 (15):1792-1798.
[106]Makela S., Savolainen H., Aavik E., et al. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta[J]. Proc Natl Acad Sci U S A,1999,96 (12):7077-7082.
[107]Lou H., Martin M. B., Stoica A., et al. Upregulation of estrogen receptor-alpha expression in rabbit cardiac allograft[J]. Circ Res,1998,83 (9):947-951.
[108]Zhai P., Eurell T. E., Cooke P. S., et al. Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice[J]. Am J Physiol Heart Circ Physiol, 2000,278 (5):H1640-1647.
[109]Chan R. Y., Chen W. F., Dong A., et al. Estrogen-like activity of ginsenoside Rgl derived from Panax notoginseng[J]. J Clin Endocrinol Metab,2002,87 (8):3691-3695.
[110]Lau W. S., Chan R. Y., Guo D. A., et al. Ginsenoside Rgl exerts estrogen-like activities via ligand-independent activation of ERalpha pathway[J]. J Steroid Biochem Mol Biol,2008,108 (1-2):64-71.
[111]Lau W. S., Chen W. F., Chan R. Y., et al. Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rgl in human breast cancer (MCF-7) cellsLJ]. Br J Pharmacol,2009,156 (7):1136-1146.
[112]Xia Z., Vanhoutte P. M. Nitric oxide and protection against cardiac ischemia[J]. Curr Pharm Des,2011,17 (18):1774-1782.
[113]Krause B. J., Hanson M. A.,Casanello P. Role of nitric oxide in placental vascular development and function[J]. Placenta,2011,32 (11):797-805.
[114]Tousoulis D., Kampoli A. M., Tentolouris C., et al. The role of nitric oxide on endothelial function[J]. Curr Vasc Pharmacol,2012,10(1):4-18.
[115]Gkaliagkousi E., Ritter J., Ferro A. Platelet-derived nitric oxide signaling and regulation[J]. Circ Res,2007,101 (7):654-662.
[116]Ulker P., Gunduz F., Meiselman H. J., et al. Nitric oxide generated by red blood cells following exposure to shear stress dilates isolated small mesenteric arteries under hypoxic conditions[J]. Clin Hemorheol Microcirc,2012,
[117]Ulker P., Yaras N., Yalcin 0., et al. Shear stress activation of nitric oxide synthase and increased nitric oxide levels in human red blood cells[J]. Nitric Oxide, 2011,24 (4):184-191.
[118]Kim K. H., Bender J. R. Membrane-initiated actions of estrogen on the endothelium[J]. Mol Cell Endocrinol,2009,308 (1-2):3-8.
[119]Simoncini T., Rabkin E., Liao J. K. Molecular basis of cell membrane estrogen receptor interaction with phosphatidylinositol 3-kinase in endothelial cells[J]. Arterioscler Thromb Vasc Biol,2003,23 (2):198-203.
[120]Tan E., Gurjar M. V., Sharma R. V., et al. Estrogen receptor-alpha gene transfer into bovine aortic endothelial cells induces eNOS gene expression and inhibits cell migration [J]. Cardiovasc Res,1999,43 (3):788-797.
[121]Fan G., Zhu Y., Guo H., et al. Direct vasorelaxation by a novel phytoestrogen tanshinone IIA is mediated by nongenomic action of estrogen receptor through endothelial nitric oxide synthase activation and calcium mobilization[J]. J Cardiovasc Pharmacol, 2011,57 (3):340-347.
[122]Sun B., Xiao J., Sun X. B., et al. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice:an insight into oestrogen receptor activation and PI3K/Akt signalling[J]. Br J Pharmacol,2013,168 (7):1758-1770.
[123]Hien T. T., Kim N. D., Pokharel Y. R., et al. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase:Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase[J]. Toxicol Appl Pharmacol,2010,
[124]Bolt M. J., Stossi F., Newberg J. Y., et al. Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses[J]. Nucleic Acids Res,2013,
[125]Kinyamu H. K..Archer T. K. Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression [J]. Mol Cell Biol,2003,23 (16):5867-5881.
[126]Attele A. S., Wu J. A., Yuan C. S. Ginseng pharmacology:multiple constituents and multiple actions[J]. Biochem Pharmacol,1999,58 (11):1685-1693.
[127]Lee Y. J., Chung E., Lee K. Y., et al. Ginsenoside-Rgl, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor [J]. Mol Cell Endocrinol,1997,133 (2):135-140.
[128]Zhou H., Hou S. Z., Luo P., et al. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism[J]. J Ethnopharmacol,2011,135 (2):287-298.
[129]Poellinger L. Mechanistic aspects--the dioxin (aryl hydrocarbon) receptor[J]. Food Add it Contam,2000,17 (4):261-266.
[130]Safe S..McDougal A. Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review) [J]. Int J Oncol,2002,20 (6):1123-1128.
[131]Safe S., Wormke M. Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action[J]. Chem Res Toxicol,2003,16 (7):807-816.
[132]Nebert D. W., Dalton T. P., Okey A. B., et al. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer [J]. J Biol Chem,2004,279 (23):23847-23850.
[133]Gharavi N., El-Kadi A.0. Down-regulation of aryl hydrocarbon receptor-regulated genes by tumor necrosis factor-alpha and lipopolysaccharide in murine hepatoma Hepa 1clc7 cells[J]. J Pharm Sci,2005,94 (3):493-506.
[134]Walisser J. A., Bunger M. K., Glover E., et al. Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development [J]. Proc Natl Acad Sci U S A,2004, 101 (47):16677-16682.
[135]Madak-Erdogan Z., Katzenellenbogen B. S. Aryl hydrocarbon receptor modulation of estrogen receptor alpha-mediated gene regulation by a multimeric chromatin complex involving the two receptors and the coregulator RIP140[J]. Toxicol Sci,2012,125 (2): 401-411.
[136]Callero M. A., Loaiza-Perez A. I. The role of aryl hydrocarbon receptor and crosstalk with estrogen receptor in response of breast cancer cells to the novel antitumor agents benzothiazoles and aminoflavone[J]. Int J Breast Cancer,2011,2011923250.
[137]Khan S., Barhoumi R., Burghardt R., et al. Molecular mechanism of inhibitory aryl hydrocarbon receptor-estrogen receptor/Spl cross talk in breast cancer celIs[J]. Mol Endocrinol,2006,20 (9):2199-2214.
[138]Wijnen P. A., Op den Bui jsch R. A., Drent M., et al. Review article:The prevalence and clinical relevance of cytochrome P450 polymorphisms [J]. Aliment Pharmacol Ther,2007, 26 Suppl 2 211-219.
[139]朱大岭,韩维娜,张荣.细胞色素P一(450)酶系在药物代谢中的作用[J].医药导报,2004,23(7)：440-443.
[140]张虹,范婷婷,方昱.细胞色素P450 3A4的研究进展[J].中国医院药学杂志,2009,29(4)：317-320.
[141]陈欣,李玉珍,方翼.CYP3A4代谢药物的特点及其多态性的研究现状[J].中国药房,2010,21(22)：2097-2099.
[142]Rendie S., Di Carlo F. J. Human cytochrome P450 enzymes:a status report summarizing their reactions, substrates, inducers, and inhibitors [J]. Drug Metab Rev,1997,29 (1-2): 413-580.
[143]Paine M. F., Khalighi M., Fisher J. M., et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism[J]. J Pharmacol Exp Ther,1997,283 (3):1552-1562.
[144]Kato M. Intestinal first-pass metabolism of CYP3A4 substrates[J]. Drug Metab Pharmacokinet,2008,23 (2):87-94.
[145]鞠美华.细胞色素P450同工酶在外源物代谢中的作用[J].国外医学.药学分册,1998,25(4)：218-224.
[146]李越,李燕.孕烷x受体对细胞色素P4503A调控机制的研究进展[J].国际药学研究杂志,2009,36(3)：184-188.
[147]Zhang Y., Huang L., Bi H., et al. Study of the upregulation of the activity of cytochrome P450 3A isoforms by Astragalus injection and Astragalus granules in rats and in cells [J]. Eur J Drug Metab Pharmacokinet,2012,
[148]Malati C. Y., Robertson S. M., Hunt J. D., et al. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants [J]. J Clin Pharmacol,2012,52 (6):932-939.
[149]Li Y., Wang Q., Yao X. Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor-and pregnane X receptor-mediated pathways [J]. Eur J Pharmacol,2010,640 (1-3): 46-54.
[150]Yu C., Ye S., Sun H., et al. PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA[J]. Chem Biol Interact,2009,177 (1):58-64.
[151]董海燕,邵敬伟,王涛,等.四种抗癌中药提取物对大鼠肝CYP3A酶活性及mRNA表达的影响[J].中药材,2008,31(1)：68-71.
[152]Pao L. H., Hu 0. Y., Fan H. Y., et al. Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo[J]. Am J Chin Med,2012,40 (1):57-73.
[153]Liu Y., Zhang J. W., Li W., et al. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes [J]. Toxicol Sci,2006,91 (2):356-364.
[154]He N.,Edeki T. The inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes[J]. Am J Ther,2004,11 (3):206-212.
[155]A unified nomenclature system for the nuclear receptor superfamily[J]. Cell,1999, 97 (2):161-163.
[156]胡承,贾伟平.PPAR δ与脂代谢及胰岛素抵抗[J].国际内分泌代谢杂志,2006,26(6)：385-387.
[157]Higashiyama H., Billin A. N., Okamoto Y., et al. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray[J]. Histochem Cell Biol,2007,127 (5):485-494.
[158]Bojic L. A., Sawyez C. G., Telford D. E., et al. Activation of peroxisome proliferator-activated receptor delta inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein[J]. Arterioscler Thromb Vasc Biol,2012,32 (12):2919-2928.
[159]Brown J. D., Oligino E., Rader D. J., et al. VLDL hydrolysis by hepatic lipase regulates PPARdelta transcriptional responses[J]. PLoS One,2011,6 (7):e21209.
[160]Benetti E., Patel N. S..Collino M. The role of PPARbeta/delta in the management of metabolic syndrome and its associated cardiovascular complications [J]. Endocr Metab Immune Disord Drug Targets,2011,11 (4):273-284.
[161]Krogsdam A. M., Nielsen C. A., Neve S., et al. Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation[J]. Biochem J,2002,363 (Pt 1):157-165.
[162]Shi Y., Hon M., Evans R. M. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling [J]. Proc Natl Acad Sci U S A,2002,99 (5):2613-2618.
[163]Ruan X., Zheng F., Guan Y. PPARs and the kidney in metabolic syndrome[J]. Am J Physiol Renal Physiol,2008,294 (5):F1032-1047.
[164]Abdelrahman M., Sivarajah A., Thiemermann C. Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock [J]. Card iovasc Res,2005, 65 (4):772-781.
[165]Diradourian C., Girard J., Pegorier J. P. Phosphorylation of PPARs:from molecular characterization to physiological relevance[J]. Biochimie,2005,87 (1):33-38.
[166]Moraes L. A., Swales K. E., Wray J. A., et al. Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets [J]. Blood,2007,109 (9): 3741-3744.
[167]Gao L., Tao Y., Zhang L, et al. Vitamin D receptor genetic polymorphisms and tuberculosis:updated systematic review and meta-analysis[J]. Int J Tuberc Lung Dis,2010, 14 (1):15-23.
[168]Wu-Wong J. R. Potential for vitamin D receptor,agonists in the treatment of cardiovascular disease[J]. Br J Pharmacol,2009,158 (2):395-412.
[169]Sertznig P., Seifert M., Tilgen W., et al. Activation of vitamin D receptor (VDR)-and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines[J]. Dermatoendocrinol,2009,1 (4):232-238.
[170]McHowat J.,Creer M. H. Catalytic features, regulation and function of myocardial phospholipase A2[J]. Curr Med Chem Cardiovasc Hematol Agents,2004,2 (3):209-218.
[171]Caslake M. J., Packard C. J., Suckling K. E., et al. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase:a potential new risk factor for coronary artery disease[J]. Atherosclerosis,2000,150 (2):413-419.
[172]Wang Q., Hao Y., Mo X., et al. PLA2G7 gene polymorphisms and coronary heart disease risk:a meta-analysis[J]. Thromb Res,2010,126 (6):498-503.
[173]Packard C. J., O'Reilly D. S., Caslake M. J., et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group[J]. N Engl J Med,2000,343 (16):1148-1155.
[174]Jenkins C. M., Cedars A., Gross R. W. Eicosanoid signalling pathways in the heart [J]. Cardiovasc Res,2009,82 (2):240-249.
[175]Michalski L., Kleniewska P., Piechota-Polanczyk A., et al. The role of endothelin-1 and its receptor blockers on the liver function[J]. Gen Physiol Biophys,2012,31 (4): 383-388.
[176]Pernow J., Shemyakin A., Bohm F. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus[J]. Life Sci,2012,91 (13-14):507-516.
[177]Simeone S. M., Li M. W., Paradis P., et al. Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium[J]. Physiol Genomics,2011, 43 (3):148-160.
[178]Takakuwa T., Endo S., Nakae H., et al. Relationship between plasma levels of type Ⅱ phospholipase A2, PAF acetylhydrolase, endothelin-1, and thrombomodulin in patients with infected burns[J]. Res Commun Mol Pathol Pharmacol,1994,86 (3):335-340.
[179]Yousufzai S. Y., Abdel-latif A. A. Endothelin-1 stimulates the release of arachidonic acid and prostaglandins in cultured human ciliary muscle cells:activation of phospholipase A2[J]. Exp Eye Res,1997,65 (1):73-81.
[180]Romanelli F., Fillo S., Isidori A., et al. Stimulatory action of endothelin-1 on rat Leydig cells:involvement of endothelin-A subtype receptor and phospholipase A2-arachidonate metabolism system[J]. Life Sci,1997,61 (5):557-566.
[181]Kieffer B. L. Opioids:first lessons from knockout mice[J]. Trends Pharmacol Sci, 1999,20 (1):19-26.
[182]Matthes H. W., Maldonado R., Simonin F., et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene[J]. Nature,1996,383 (6603):819-823.
[183]Simon E. J. Subunit structure and purification of opioid receptors[J]. J Recept Res,1987,7 (1-4):105-132.
[184]吴符火,刘雪酶,贾铷.丹七胶囊的药效学研究[J].中国中药杂志,2005,30(23)：1869-1873.
[185]毛春芹,陆兔林,邱鲁婴.三棱不同炮制品总黄酮镇痛作用研究[J].南京中医药大学学报(自然科学版),2001,17(5)：299-300.
[186]鲁汉兰,彭智聪,刘勇,等.莪术炮制后对止痛及活血化瘀作用的影响[J].中成药,2000,22(2)：27-29.
[187]王一菱, 陈迪,吴景兰.三七总皂甙抗炎和镇痛作用及其机理探讨[J].中国中西医结合杂志,1994,14(1)：35-36,35-36.
[188]Li Z., Li L., Zielke H. R., et al. Increased expression of 72-kd type IV collagenase (MMP-2) inhuman aortic atherosclerotic lesions[J]. Am J Pathol,1996,148 (1):121-128.
[189]Alp E., Menevse S., Tulmac M., et al. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction[J]. Genet Test Mol Biomarkers,2011,15 (4):193-202.
[190]Pasterkamp G., Schoneveld A. H., Hijnen D. J., et al. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1,2 and 9 in the human coronary artery[J]. Atherosclerosis,2000,150 (2):245-253.
[191]Fert-Bober J., Leon H., Sawicka J., et al. Inhibiting matrix metalloproteinase-2 reduces protein release into coronary effluent from isolated rat hearts during ischemia-reperfusion[J]. Basic Res Cardiol,2008,103 (5):431-443.
[192]Dhillon O. S., Khan S. Q., Narayan H. K., et al. Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome[J]. Clin Sci (Lond),2010,118 (4): 249-257.
[193]Clark A. W., Krekoski C. A., Bou S. S., et al. Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia[J]. Neurosci Lett, 1997,238 (1-2):53-56.
[194]王凤,金笑平.基质金属蛋白酶2及其基因多态性与动脉粥样硬化的关系[J].医学综述,2010,16(20)：3041-3043.
[195]Grote K., Flach I., Luchtefeld M., et al. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species[J]. Circ Res,2003,92 (11):e80-86.
[196]Dai Y., Bae K., Siemann D. W. Impact of hypoxia on the metastatic potential of human prostate cancer cells[J]. Int J Radiat Oncol Biol Phys,2011,81 (2):521-528.
[197]Lim C. S., Qiao X., Reslan 0. M., et al. Prolonged mechanical stretch is associated with upregulation of hypoxia-inducible factors and reduced contraction in rat inferior vena cava[J]. J Vasc Surg,2011,53 (3):764-773.
[198]Jovanovic M., Stefanoska I., Radojcic L., et al. Interleukin-8 (CXCL8) stimulates trophoblast cell migration and invasion by increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins alpha5 and betal[J]. Reproduction,2010,139 (4):789-798.
[199]Mulayim N., Savlu A., Guzeloglu-Kayisli 0., et al. Regulation of endometrial stromal cell matrix metalloproteinase activity and invasiveness by interleukin-8[J]. Fertil Steril,2004,81 Suppl 1904-911.
[200]许晓乐,季晖,谷舒怡,等.黄芪甲苷对小鼠实验性心室重构及基质金属蛋白酶表达的影响[J].中国药科大学学报,2010,41(1)：70-75.
[201]殷春嫒.黄芪对兔动脉粥样硬化模型基质金属蛋白酶-2,9的抑制作用.硕士论文.吉林大学,27,2009.
[202]石耀辉.人参皂苷Rb3对大鼠心肌缺血再灌注损伤的保护作用及其对大鼠心肌梗死不同阶段基质金属蛋白酶的影响.博士论文.吉林大学,77,2012.
[203]Curry S. Lessons from the crystallographic analysis of small molecule binding to human serum albumin[J]. Drug Metab Pharmacokinet,2009,24 (4):342-357.
[204]Tamion F. [Albumin in sepsis][J]. Ann Fr Anesth Reanim,2010,29 (9):629-634.
[205]Donadio C., Tognotti D., Donadio E. Albumin modification and fragmentation in renal disease[J]. Clin Chim Acta,2012,413 (3-4):391-395.
[206]Roche M., Rondeau P., Singh N. R., et al. The antioxidant properties of serum albumin[J]. FEBS Lett,2008,582 (13):1783-1787.
[207]杜卫东,叶再元,徐旭军.人参皂甙对腹腔感染大鼠血清白蛋白的影响[J].浙江中医学院学报,2003,(2)：58-59.
[208]Wang M., Wang Y., Weil B., et al. Estrogen receptor beta mediates increased activation of PI3K/Akt signaling and improved myocardial function in female hearts following acute ischemia[J]. Am J Physiol Regul Integr Comp Physiol,2009,296 (4): R972-978.
[209]Haynes M. P., Li L., Sinha D., et al. Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen[J]. J Biol Chem,2003,278 (4):2118-2123.
[210]Martignoni M., Groothuis G. M., de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction[J]. Expert Opin Drug Metab Toxicol,2006,2 (6):875-894.
[211]Imai J., Ieiri I., Mamiya K., et al. Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients:genetic analysis of the CYP2C9 locus[J]. Pharmacogenetics,2000,10 (1):85-89.
[212]Hirota T., Eguchi S., Ieiri I. Impact of Genetic Polymorphisms in CYP2C9 and CYP2C19 on the Pharmacokinetics of Clinically Used Drugs [J]. Drug Metab Pharmacokinet,2013,28 (1):28-37.
[213]Wilkinson G. R., Guengerich F. P., Branch R. A. Genetic polymorphism of S-mephenytoin hydroxylation[J]. Pharmacol Ther,1989,43 (1):53-76.
[214]Andersson T., Regardh C. G., Lou Y. C., et al. Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects[J]. Pharmacogenetics,1992,2 (1):25-31.
[215]Sindrup S. H., Brosen K., Hansen M. G., et al. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms [J]. Ther Drug Monit, 1993,15 (1):11-17.
[216]Bertilsson L., Henthorn T. K., Sanz E., et al. Importance of genetic factors in the regulation of diazepam metabolism:relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype[J]. Clin Pharmacol Ther,1989,45 (4):348-355.
[217]Shu Y., Wang L. S., Xiao W. M., et al. Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone[J]. Acta Pharmacol Sin,2000,21 (8):753-758.
[218]何楠,周宏灏CYP2C19遗传多态性的研究进展[J].生理科学进展,2003,34(2)：171-174.
[219]毕惠嫦,和凡,温莹莹,等.丹参酮II_A在大鼠肝微粒体酶中的代谢动力学[J].中草药,2007,38(6)：882-886.
[220]赵慧娟.中药对大鼠CYP2D6、CYP1A2和CYP2C19的抑制作用.硕士论文.郑州大学,38.2009.
[221]马萍,胡荣,王小英,等.中药人参治疗糖尿病的研究进展[J].湖北中医药大学学报,2013,15(1)：63-65.
[222]杨晓,蒋丽平,王书.黄芪多糖对高脂血症大鼠血脂、免疫功能及氧化应激指标的影响[J].现代中药研究与实践,2012,26(5)：37-40.
[223]贡云华,蒋家雄,李泽,等.三七皂甙C1对四氧嘧啶糖尿病小鼠的降血糖作用[J].药学学报,1991,26(2)：81-85.
[1]衷敬柏,董绍英,王阶,等.2689例冠心病心绞痛证候要素的文献统计分析[J].中国中医药信息杂志,2006,13(5)：100-101.
[2]何庆勇,王阶,张允岭,等.冠心病介入术后再狭窄危险因素及中医证候要素分析[J].北京中医药大学学报,2008,31(8)：569-572.
[3]张秋雁,邓冰湘.冠心病心绞痛临床中医证型分布的回顾性分析[J].中医研究,2005,18(11)：23-24.
[4]陈世宏,叶耘,尚正录,等.黄芪保心汤对缺血心肌心功能及心肌细胞超微结构的影响[J].中华中医药学刊,2008,26(2)：376-378.
[5]姜浩,农一兵,林谦.益气活血药对心梗后心功能不全大鼠心肌细胞RYR2、SERCA2a及PLBmRNA表达的影响[J].中华中医药杂志,2011,26(9)：1957-1960.
[6]尹慧秋,张继东,乔云,等.舒脉胶囊对心肌缺血大鼠心肌细胞凋亡的影响[J].山东大学学报(医学版),2007,179(7)：739-742.
[7]李敏,王硕仁,赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响[J].中西医结合心脑血管病杂志,2005,3(1)：33-35.
[8]杨建飞,杨颖,孙静,等.人参黄芪含药血清对人脐静脉内皮细胞活性的影响[J].中医药信息,2012,29(2)：21-23.
[9]励石寒,卢慧勤,陈孝.参芪培元口服液保护急性心肌缺血损伤的机制研究[J].中国药师,2004,7(10)：747-749.
[10]赵贵起,周爱民,李秀军,等.补阳还五汤对高脂血症大鼠血流变及血清一氧化氮的影响[J].河北中医,2009,31(6)：911-913.
[11]宫爱华,孙素琴,荣文平.心痛滴剂治疗冠心病心绞痛的实验研究[J].辽宁中医杂志,2004,31(5)：434-435.
[12]章怡祎,刘萍,高虹,等.冠心康对脂质损伤的人血管内皮细胞保护机制的研究[J].中医药学刊,2005,23(8)：1418-1419.
[13]侯霄雷,李白翎,赵雷,等.血府逐瘀胶囊对急性心肌梗死再灌注后心肌及内皮素-1、一氧化氮／一氧化氮合酶体系影响的实验研究[J].中西医结合学报,2008,6(4)：381-386.
[14]韩旭,李七一,夏卫军,等.通心络胶囊对载脂蛋白E基因敲除小鼠冠状动脉粥样硬化的影响及其机理研究[J].中国中医药信息杂志,2011,18(2)：37-40.
[15]吴爱明,张冬梅,娄利霞,等.生脉注射液联合血塞通注射液对心肌梗死大鼠室颤阈值和心肌连接蛋白43表达的影响[J].中西医结合学报,2011,9(7)：775-782.
[16]张会超,韩丽华,王振涛,等.益气活血方对心梗后左室重构大鼠心肌基质金属蛋白酶-2、转化生长因子-β_1的影响[J].中成药,2010,32(11)：1871-1874.
[17]姜大伟,赵学忠,于晓风,等.西洋参茎叶三醇组皂苷对大鼠压力超负荷性心室重构的保护作用[J].中华老年医学杂志,2011,11(30)：953-957.
[18]韩冬,于晓风,曲绍春,等.人参皂苷Rb_3对大鼠实验性心室重构的影响及其机制[J].吉林大学学报(医学版),2010,36(6)：1047-105 I+1993.
[19]卢应,董均树,刘娅,等.西洋参叶20S-原人参二醇组皂苷对大鼠实验性心室重构的影响[J].中草药,2009,40(11)：1785-1787.
[20]张志毅,梅轶芳,赵彦萍,等.益气活血化痰法中药对泡沫细胞基质金属蛋白酶1/2mRNA表达的影响[J].中国中西医结合急救杂志,2005,12(4)：238-241.
[21]刘月玲,朱秋玲.参七粉对动脉粥样硬化家兔血脂代谢及血管内皮功能的影响[J].中国医药导报,2012,9(6)：26-28.
[22]肖纯,孙明,金益强,等.通脉颗粒对兔动脉粥样硬化模型血脂水平及主动脉和冠状动脉病变的影响[J].中国动脉硬化杂志,2005,13(6)：705-708.
[23]姜丽红,陈立红.益气活血方对实验性心肌梗死大鼠心肌梗死面积及VEGF、bFGF、Ⅷ表达量的影响[J].世界中西医结合杂志,2011,6(12)：1067-1070.
[24]王振涛,王硕仁,赵明镜,等.活血、益气方药对心梗后左心衰大鼠血TNF和血小板聚集影响的对比研究[J].中国中医药信息杂志,2002,9(11)：20-22.
[25]钟超,夏承来.丹参酮II_A对大鼠血管内皮细胞血栓调节蛋白表达的影响[J].中药材,2010,33(3)：425-427.
[26]李响,张愚,马雪涛,等.注射用血栓通对白细胞黏附及相关黏附分子表达影响的体外实验研究[J].中华中医药学刊,2009,27(10)：2200-2202.
[2]吴临爱.冠心病临床流行病学调查及干预对策[J].山西医药杂志(下半月刊),2012,41(5)：452-454.
[3]滕龙,洪芳,何建成.冠心病中医证候微观诊断指标的研究进展[J].时珍国医国药,2012,23(12)：3119-3121.
[4]王少青,刘朋,刘颖,等.复方丹参滴丸抗动脉粥样硬化研究进展[J].中国新药杂志,2012,21(15)：1765-1768.
[5]周忠冉,唐海沁,李结华,等.通心络胶囊治疗冠心病疗效及安全性的系统评价[J].中国循证医学杂志,2011,11(9)：1078-1083.
[6]姚惠,郑培奋,陈建明,等.丹参川芎汤辨证治疗老年气阴两虚血瘀型冠心病的临床疗效分析[J].浙江中医药大学学报,2012,36(12)：1312-1314.
[7]陈会君,周亚滨,王岩.养心汤治疗冠心病不稳定型心绞痛经验撷菁[J].辽宁中医药大学学报,2012,14(12)：60-61.
[8]薛为民,陆玉昌.文本挖掘技术研究[J].北京联合大学学报(自然科学版),2005,19(4)：59-63.
[9]Luscombe N. M., Greenbaum D., Gerstein M. What is bio informatics? A proposed definition and overview of the field[J]. Methods Inf Med,2001,40 (4):346-358.
[10]王非.中药现代化的EXPRESSWAY——利用生物信息学推动中药现代化[J].中国处方药,2002,(7)：44-46.
[11]Zheng G., Jiang M., He X., et al. Discrete derivative:a data slicing algorithm for exploration of sharing biological networks between rheumatoid arthritis and coronary heart disease[J]. BioData Min,2011,418.
[12]宋燕青,徐向阳,孙仁弟.注射用丹参多酚酸盐的临床应用概述[J].药物流行病学杂志,2012,21(8)：404-407.
[13]刘芳,戴小华.益气活血中药改善冠心病患者血管内皮功能临床研究进展[J].中医药临床杂志,2012,1(24)：
[14]李伟.丹参注射液治疗冠心病心绞痛的疗效分析[J].中国当代医药,2011,18(31)：72,74.
[15]黄海波,李彦会,王文星,等.三七心血通胶囊治疗痰阻心脉型冠心病心绞痛临床观察[J].河北中医,2012,34(7)：987-988.
[16]郭洪涛,郑光,赵静,等.基于文本挖掘分析甲型H1N1流感的中医药治疗特色[J].世界科学技术(中医药现代化),2011,13(5)：772-776.
[17]吴焕林,王侠,李晓庆.126例急性心肌梗死病人证候特点的回顾性分析[J].辽宁中医杂志,2010,37(9)：1749-1750.
[18]郑国华,熊尚全,周锟,等.福州地区507例汉族冠心病患者中医证型分布规律研究[J].中国中西医结合杂志,2011,31(6)：756-759.
[19]葛永彬,毛静远.7512例冠心病中医证型分布规律分析[J].山东中医杂志,2011,30(4)：227-229.
[20]毛静远,牛子长,张伯礼.近40年冠心病中医证候特征研究文献分析[J].中医杂志,2011,52(11)：958-961.
[21]刘陶世,黄耀洲.丹参成分、制剂和质量控制研究概况[J].南京中医药大学学报,1998,14(4)：66-67.
[22]林峰,石杰.丹参活性成分的药效药理作用[J].医学信息(上旬刊),2011,24(6)：3813-3814.
[23]高传长,邹书兵.丹参及其主要成分在冠心病及胰腺炎等疾病中的治病机制[J].中国中西医结合杂志,2010,30(11)：1222-1227.
[24]张喜平,齐丽丽,刘达人.三七及其有效成分的药理作用研究现状[J].医学研究杂志,2007,36(4)：96-98.
[25]蔡广,叶常青,许祯,等.三七总甙注射液治疗冠心病的疗效[J].心脏杂志,2006,18(5)：562-564+567.
[26]邱勇波,刘锦,武飞.黄芪化学成分及药理作用研究进展[J].中国疗养医学,2011,20(5)：435-436.
[27]张蔷,高文远,满淑丽.黄芪中有效成分药理活性的研究进展[J].中国中药杂志,2012,37(21)：3203-3207.
[28]郭秀丽,高淑莲.人参化学成分和药理研究进展[J].中医临床研究,2012,4(14)：26-27.
[29]王悦虹,娄大伟,于晓洋,等.人参的药理学作用研究进展[J].吉林化工学院学报,2010,27(2)：38-41.
[30]张念志,韩明向,周宜轩,等.人参注射液对冠心病心绞痛心气虚证作用的临床研究[J].中国中医急症,2000,9(4)：141-136.
[31]丘瑞香,金明华,吴国珍.人参对老年冠心病肾虚患者性激素双向调节的研究[J].中医杂志,1997,38(11)：672-674.
[32]赵熙灼,梁炳圻,洪行球,等.人参芦皂甙治疗冠心病的临床研究——294例报告[J].中药药理与临床,1991,7(5)：34-37.
[33]王薇娜,赵良平,王丽,等.人参皂甙Rb_1对大鼠急性心肌梗死后左室重构的影响[J].中国微循环,2006,10(4)：256-258.
[34]谢海波,莫新民,罗尧岳.活血药、破血药对动脉粥样硬化大鼠血脂、血液流变学的影响[J].湖南中医药大学学报,2010,30.(3)：20-22.
[35]钱伟,赵福海,史大卓.莪术及其提取物的心血管药理研究进展[J].中国中西医结合杂志,2012,32(4)：575-576.
[36]和岚,张秀梅,毛腾敏.三棱、丹参对血液流变学影响的比较研究[J].山东中医药大学学报,2007,31(5)：434-435.
[37]李建民.三棱莪术汤治疗冠心病稳定型心绞痛临床观察[J].天津中医药,2007,24(6)：470-471.
[38]许忠能.生物信息学发展与中草药研究[J].中草药,2003,34(6)：481-486.
[39]孙排正.镍离子细胞毒性差异表达基因生物信息学分析.硕士论文.东南大学,84-90.2008,
[40]Greer S. N., Metcalf J. L., Wang Y., et al. The updated biology of hypoxia-inducible factor[J]. EMBO J,2012,31 (11):2448-2460.
[41]Wang G. L., Jiang B. H., Rue E. A., et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular 02 tension[J]. Proc Natl Acad Sci U S A,1995,92 (12):5510-5514.
[42]Wang G. L.,Semenza G. L. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia[J]. J Biol Chem,1993,268 (29): 21513-21518.
[43]Dayan F., Roux D., Brahimi-Horn M. C., et al. The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-lalpha[J]. Cancer Res,2006,66 (7):3688-3698.
[44]Jiang B. H., Zheng J. Z., Leung S. W., et al. Transactivation and inhibitory domains of hypoxia-inducible factor lalpha. Modulation of transcriptional activity by oxygen tension[J]. J Biol Chem,1997,272 (31):19253-19260.
[45]Huang L. E., Gu J., Schau M., et al. Regulation of hypoxia-inducible factor lalpha is mediated by an 02-dependent degradation domain via the ubiquitin-proteasome pathway [J]. Proc Natl Acad Sci U S A,1998,95 (14):7987-7992.
[46]Poon E., Harris A. L., Ashcroft M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer[J]. Expert Rev Mol Med,2009,11 e26.
[47]Semenza G. L. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J]. Oncogene,2010,29 (5):625-634.
[48]Ivan M., Kondo K., Yang H., et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation:implications for 02 sensing[J]. Science,2001,292 (5516): 464-468.
[49]Jaakkola P., Mole D. R., Tian Y. M., et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by 02-regulated prolyl hydroxylation[J]. Science, 2001,292 (5516):468-472.
[50]Masson N., Willam C., Maxwell P. H., et al. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation[J]. EMBO J,2001,20 (18):5197-5206.
[51]Ahluwalia A..Tarnawski A. S. Critical role of hypoxia sensor--HIF-lalpha in VEGF gene activation. Implications for angiogenesis and tissue injury healing[J]. Curr Med Chem,2012,19 (1):90-97.
[52]Date T., Mochizuki S., Belanger A. J., et al. Expression of constitutively stable hybrid hypoxia-inducible factor-lalpha protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury[J]. Am J Physiol Cell Physiol,2005,288 (2): C314-320.
[53]Dendorfer A., Heidbreder M., Hellwig-Burgel T., et al. Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals[J]. Free Radic Biol Med,2005,38 (1):117-124.
[54]Ockaili R., Natarajan R., Salloum F., et al. HIF-1 activation attenuates postischemic myocardial injury:role for heme oxygenase-1 in modulating microvascular chemokine generation[J]. Am J Physiol Heart Circ Physiol,2005,289 (2):H542-548.
[55]Belaidi E., Beguin P. C., Levy P., et al. Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium results in loss of myocardial hypoxic preconditioning in the rat[J]. Am J Physiol Heart Circ Physiol,2008,294 (2):H901-908.
[56]Natarajan R., Salloum F. N., Fisher B. J., et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury [J]. J Cardiovasc Pharmacol,2008,51 (2):178-187.
[57]Tekin D., Dursun A. D., Xi L. Hypoxia inducible factor 1 (HIF-1) and cardioprotection[J]. Acta Pharmacol Sin,2010,31 (9):1085-1094.
[58]Ong S. G., Hausenloy D. J. Hypoxia-inducible factor as a therapeutic target for cardioprotection[J]. Pharmacol Ther,2012,136 (1):69-81.
[59]Blagosklonny M. V., An W. G., Romanova L. Y., et al. p53 inhibits hypoxia-inducible factor-stimulated transcription[J]. J Biol Chem,1998,273 (20):11995-11998.
[60]Suzuki H., Tomida A., Tsuruo T. Dephosphorylated hypoxia-inducible factor lalpha as a mediator of p53-dependent apoptosis during hypoxia[J]. Oncogene,2001,20 (41): 5779-5788.
[61]Semenza G. L. Regulation of oxygen homeostasis by hypoxia-inducible factor 1[J]. Physiology (Bethesda),2009,24 97-106.
[62]Loor G., Schumacker P. T. Role of hypoxia-inducible factor in cell survival during myocardial ischemia-reperfusion[J]. Cell Death Differ,2008,15 (4):686-690.
[63]Zachary I., Mathur A., Yla-Herttuala S., et al. Vascular protection:A novel nonangiogenic cardiovascular role for vascular endothelial growth factor[J]. Arterioscler Thromb Vasc Biol,2000,20 (6):1512-1520.
[64]Inoue M., Itoh H., Ueda M., et al. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions:possible pathophysiological significance of VEGF in progression of atherosclerosis[J]. Circulation,1998,98 (20): 2108-2116.
[65]Banai S., Jaklitsch M. T., Shou M., et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs[J]. Circulation,1994,89 (5):2183-2189.
[66]Oloumi A., Syam S., Dedhar S. Modulation of Wnt3a-mediated nuclear beta-catenin accumulation and activation by integrin-linked kinase in mammalian cells[J]. Oncogene, 2006,25 (59):7747-7757.
[67]Cho H. J., Youn S. W., Cheon S. I., et al. Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase[J]. Arterioscler Thromb Vasc Biol,2005,25 (6):1154-1160.
[68]Traister A., Aafaqi S., Masse S., et al. ILK induces cardiomyogenesis in the human heart[J]. PLoS One,2012,7 (5):e37802.
[69]Tseng W. P., Yang S. N., Lai C. H., et al. Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts[J]. J Cell Physiol,2010,223 (3):810-818.
[70]Leyme A., Bourd-Boittin K., Bonnier D., et al. Identification of ILK as a new partner of the ADAM12 disintegrin and metalloprotease in cell adhesion and survival [J]. Mol Biol Cell,2012,23 (17):3461-3472.
[71]Wani A. A., Jafarnejad S. M., Zhou J., et al. Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kappaB/interleukin-6 signaling pathway[J]. Oncogene,2011,30 (24):2778-2788.
[72]Tan C., Cruet-Hennequart S., Troussard A., et al. Regulation of tumor angiogenesis by integrin-linked kinase (ILK)[J]. Cancer Cell,2004,5 (1):79-90.
[73]Ding L., Dong L., Chen X., et al. Increased expression of integrin-linked kinase attenuates left ventricular remodeling and improves cardiac function after myocardial infarction[J]. Circulation,2009,120 (9):764-773.
[74]Bendig G., Grimmler M., Huttner I. G., et al. Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart[J]. Genes Dev,2006,20 (17):2361-2372.
[75]Moeller L. C., Broecker-Preuss M. Transcriptional regulation by nonclassical action of thyroid hormone[J]. Thyroid Res,2011,4 Suppl 1 S6.
[76]Moeller L. C., Cao X., Dumitrescu A. M., et al. Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway[J]. Nucl Recept Signal,2006,4 e020.
[77]薛增明,马长生.甲状腺激素降低与心血管疾病[J].中国实用内科杂志,2012,32(10)：804-806.
[78]Singh S., Duggal J., Molnar J., et al. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality:a meta-analysis[J]. Int J Cardiol,2008,125 (1):41-48.
[79]Coceani M., Iervasi G., Pingitore A., et al. Thyroid hormone and coronary artery disease:from clinical correlations to prognostic implications[J]. Clin Cardiol,2009, 32 (7):380-385.
[80]Rodondi N., Aujesky D., Vittinghoff E., et al. Subclinical hypothyroidism and the risk of coronary heart disease:a meta-analysis[J]. Am J Med,2006,119 (7):541-551.
[81]Kong H. L., Wang J. P., Li Z. Q., et al. Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo[J]. Acta Pharmacol Sin,2009,30 (4):396-403.
[82]Leung K. W., Ng H. M., Tang M. K., et al. Ginsenoside-Rgl mediates a hypoxia-independent upregulation of hypoxia-inducible factor-lalpha to promote angiogenesis[J]. Angiogenesis,2011,14 (4):515-522.
[83]Shen K., Ji L., Gong C., et al. Notoginsenoside Ftl promotes angiogenesis via HIF-lalpha mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways[J]. Biochem Pharmacol,2012,84 (6):784-792.
[84]Xu W., Yang J.,Wu L. M. Cardioprotective effects of tanshinone IIA on myocardial ischemia injury in rats[J]. Pharmazie,2009,64 (5):332-336.
[85]Zhang L., Liu Q., Lu L., et al. Astragaloside IV stimulates angiogenesis and increases hypoxia-inducible factor-lalpha accumulation via phosphatidylinositol 3-kinase/Akt pathway[J]. J Pharmacol Exp Ther,2011,338 (2):485-491.
[86]杜雪君,雷燕,杨静.人参三七组方对急性心肌梗死大鼠缺血心肌血管内皮生长因子受体2和缺氧诱导因子1 α表达的影响[J].中西医结合学报,2010,8(6)：548-553.
[87]Deschamps A. M., Murphy E., Sun J. Estrogen receptor activation and cardioprotection in ischemia reperfusion injury[J]. Trends Cardiovasc Med,2010,20 (3):73-78.
[88]Enmark E., Gustaf sson J. A. Oestrogen receptors-an overview[J]. J Intern Med,1999, 246 (2):133-138.
[89]Shao W., Brown M. Advances in estrogen receptor biology:prospects for improvements in targeted breast cancer therapy[J]. Breast Cancer Res,2004,6 (1):39-52.
[90]Pike A. C. Lessons learnt from structural studies of the oestrogen receptor [J]. Best Pract Res Clin Endocrinol Metab,2006,20 (1):1-14.
[91]Shang Y., Hu X., DiRenzo J., et al. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription[J]. Cell,2000,103 (6):843-852.
[92]Rao B. R. Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs[J]. J Steroid Biochem Mol Biol,1998,65 (1-6):3-41.
[93]Ignar-Trowbridge D. M., Nelson K. G., Bidwell M. C., et al. Coupling of dual signaling pathways:epidermal growth factor action involves the estrogen receptor[J]. Proc Natl Acad Sci U S A,1992,89 (10):4658-4662.
[94]Kato S. Estrogen receptor-mediated cross-talk with growth factor signaling pathways[J]. Breast Cancer,2001,8 (1):3-9.
[95]Lee H., Bai W. Regulation of estrogen receptor nuclear export by ligand-induced and p38-mediated receptor phosphorylation[J]. Mol Cell Biol,2002,22 (16):5835-5845.
[96]Joel P. B., Smith J., Sturgill T. W., et al. pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167[J]. Mol Cell Biol, 1998,18 (4):1978-1984.
[97]Razandi M., Pedram A., Greene G. L., et al. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript:studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells[J]. Mol Endocrinol,1999,13 (2):307-319.
[98]Toran-Allerand C. D. Novel sites and mechanisms of oestrogen action in the brain[J]. Novartis Found Symp,2000,230 56-69; discussion 69-73.
[99]Kousteni S., Bellido T., Plotkin L. I., et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors:dissociation from transcriptional activity[J]. Cell,2001,104 (5):719-730.
[100]Yang X. P.,Reckelhoff J. F. Estrogen, hormonal replacement therapy and cardiovascular disease[J]. Curr Opin Nephrol Hypertens,2011,20 (2):133-138.
[101]Mendelsohn M. E.,Karas R. H. The protective effects of estrogen on the cardiovascular system[J]. N Engl J Med,1999,340 (23):1801-1811.
[102]Bakir S., Mori T., Durand J., et al. Estrogen-induced vasoprotection is estrogen receptor dependent:evidence from the balloon-injured rat carotid artery model[J]. Circulation,2000,101 (20):2342-2344.
[103]Chen Z., Yuhanna I. S., Galcheva-Gargova Z., et al. Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen[J]. J Clin Invest,1999,103 (3):401-406.
[104]Dubey R. K., Jackson E. K., Gillespie D. G., et al. Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity[J]. Arterioscler Thromb Vasc Biol,2000,20 (4):964-972.
[105]Hodges Y. K., Tung L., Yan X. D., et al. Estrogen receptors alpha and beta:prevalence of estrogen receptor beta mRNA in human vascular smooth muscle and transcriptional effects[J]. Circulation,2000,101 (15):1792-1798.
[106]Makela S., Savolainen H., Aavik E., et al. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta[J]. Proc Natl Acad Sci U S A,1999,96 (12):7077-7082.
[107]Lou H., Martin M. B., Stoica A., et al. Upregulation of estrogen receptor-alpha expression in rabbit cardiac allograft[J]. Circ Res,1998,83 (9):947-951.
[108]Zhai P., Eurell T. E., Cooke P. S., et al. Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice[J]. Am J Physiol Heart Circ Physiol, 2000,278 (5):H1640-1647.
[109]Chan R. Y., Chen W. F., Dong A., et al. Estrogen-like activity of ginsenoside Rgl derived from Panax notoginseng[J]. J Clin Endocrinol Metab,2002,87 (8):3691-3695.
[110]Lau W. S., Chan R. Y., Guo D. A., et al. Ginsenoside Rgl exerts estrogen-like activities via ligand-independent activation of ERalpha pathway[J]. J Steroid Biochem Mol Biol,2008,108 (1-2):64-71.
[111]Lau W. S., Chen W. F., Chan R. Y., et al. Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rgl in human breast cancer (MCF-7) cellsLJ]. Br J Pharmacol,2009,156 (7):1136-1146.
[112]Xia Z., Vanhoutte P. M. Nitric oxide and protection against cardiac ischemia[J]. Curr Pharm Des,2011,17 (18):1774-1782.
[113]Krause B. J., Hanson M. A.,Casanello P. Role of nitric oxide in placental vascular development and function[J]. Placenta,2011,32 (11):797-805.
[114]Tousoulis D., Kampoli A. M., Tentolouris C., et al. The role of nitric oxide on endothelial function[J]. Curr Vasc Pharmacol,2012,10(1):4-18.
[115]Gkaliagkousi E., Ritter J., Ferro A. Platelet-derived nitric oxide signaling and regulation[J]. Circ Res,2007,101 (7):654-662.
[116]Ulker P., Gunduz F., Meiselman H. J., et al. Nitric oxide generated by red blood cells following exposure to shear stress dilates isolated small mesenteric arteries under hypoxic conditions[J]. Clin Hemorheol Microcirc,2012,
[117]Ulker P., Yaras N., Yalcin 0., et al. Shear stress activation of nitric oxide synthase and increased nitric oxide levels in human red blood cells[J]. Nitric Oxide, 2011,24 (4):184-191.
[118]Kim K. H., Bender J. R. Membrane-initiated actions of estrogen on the endothelium[J]. Mol Cell Endocrinol,2009,308 (1-2):3-8.
[119]Simoncini T., Rabkin E., Liao J. K. Molecular basis of cell membrane estrogen receptor interaction with phosphatidylinositol 3-kinase in endothelial cells[J]. Arterioscler Thromb Vasc Biol,2003,23 (2):198-203.
[120]Tan E., Gurjar M. V., Sharma R. V., et al. Estrogen receptor-alpha gene transfer into bovine aortic endothelial cells induces eNOS gene expression and inhibits cell migration [J]. Cardiovasc Res,1999,43 (3):788-797.
[121]Fan G., Zhu Y., Guo H., et al. Direct vasorelaxation by a novel phytoestrogen tanshinone IIA is mediated by nongenomic action of estrogen receptor through endothelial nitric oxide synthase activation and calcium mobilization[J]. J Cardiovasc Pharmacol, 2011,57 (3):340-347.
[122]Sun B., Xiao J., Sun X. B., et al. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice:an insight into oestrogen receptor activation and PI3K/Akt signalling[J]. Br J Pharmacol,2013,168 (7):1758-1770.
[123]Hien T. T., Kim N. D., Pokharel Y. R., et al. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase:Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase[J]. Toxicol Appl Pharmacol,2010,
[124]Bolt M. J., Stossi F., Newberg J. Y., et al. Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses[J]. Nucleic Acids Res,2013,
[125]Kinyamu H. K..Archer T. K. Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression [J]. Mol Cell Biol,2003,23 (16):5867-5881.
[126]Attele A. S., Wu J. A., Yuan C. S. Ginseng pharmacology:multiple constituents and multiple actions[J]. Biochem Pharmacol,1999,58 (11):1685-1693.
[127]Lee Y. J., Chung E., Lee K. Y., et al. Ginsenoside-Rgl, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor [J]. Mol Cell Endocrinol,1997,133 (2):135-140.
[128]Zhou H., Hou S. Z., Luo P., et al. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism[J]. J Ethnopharmacol,2011,135 (2):287-298.
[129]Poellinger L. Mechanistic aspects--the dioxin (aryl hydrocarbon) receptor[J]. Food Add it Contam,2000,17 (4):261-266.
[130]Safe S..McDougal A. Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review) [J]. Int J Oncol,2002,20 (6):1123-1128.
[131]Safe S., Wormke M. Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action[J]. Chem Res Toxicol,2003,16 (7):807-816.
[132]Nebert D. W., Dalton T. P., Okey A. B., et al. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer [J]. J Biol Chem,2004,279 (23):23847-23850.
[133]Gharavi N., El-Kadi A.0. Down-regulation of aryl hydrocarbon receptor-regulated genes by tumor necrosis factor-alpha and lipopolysaccharide in murine hepatoma Hepa 1clc7 cells[J]. J Pharm Sci,2005,94 (3):493-506.
[134]Walisser J. A., Bunger M. K., Glover E., et al. Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development [J]. Proc Natl Acad Sci U S A,2004, 101 (47):16677-16682.
[135]Madak-Erdogan Z., Katzenellenbogen B. S. Aryl hydrocarbon receptor modulation of estrogen receptor alpha-mediated gene regulation by a multimeric chromatin complex involving the two receptors and the coregulator RIP140[J]. Toxicol Sci,2012,125 (2): 401-411.
[136]Callero M. A., Loaiza-Perez A. I. The role of aryl hydrocarbon receptor and crosstalk with estrogen receptor in response of breast cancer cells to the novel antitumor agents benzothiazoles and aminoflavone[J]. Int J Breast Cancer,2011,2011923250.
[137]Khan S., Barhoumi R., Burghardt R., et al. Molecular mechanism of inhibitory aryl hydrocarbon receptor-estrogen receptor/Spl cross talk in breast cancer celIs[J]. Mol Endocrinol,2006,20 (9):2199-2214.
[138]Wijnen P. A., Op den Bui jsch R. A., Drent M., et al. Review article:The prevalence and clinical relevance of cytochrome P450 polymorphisms [J]. Aliment Pharmacol Ther,2007, 26 Suppl 2 211-219.
[139]朱大岭,韩维娜,张荣.细胞色素P一(450)酶系在药物代谢中的作用[J].医药导报,2004,23(7)：440-443.
[140]张虹,范婷婷,方昱.细胞色素P450 3A4的研究进展[J].中国医院药学杂志,2009,29(4)：317-320.
[141]陈欣,李玉珍,方翼.CYP3A4代谢药物的特点及其多态性的研究现状[J].中国药房,2010,21(22)：2097-2099.
[142]Rendie S., Di Carlo F. J. Human cytochrome P450 enzymes:a status report summarizing their reactions, substrates, inducers, and inhibitors [J]. Drug Metab Rev,1997,29 (1-2): 413-580.
[143]Paine M. F., Khalighi M., Fisher J. M., et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism[J]. J Pharmacol Exp Ther,1997,283 (3):1552-1562.
[144]Kato M. Intestinal first-pass metabolism of CYP3A4 substrates[J]. Drug Metab Pharmacokinet,2008,23 (2):87-94.
[145]鞠美华.细胞色素P450同工酶在外源物代谢中的作用[J].国外医学.药学分册,1998,25(4)：218-224.
[146]李越,李燕.孕烷x受体对细胞色素P4503A调控机制的研究进展[J].国际药学研究杂志,2009,36(3)：184-188.
[147]Zhang Y., Huang L., Bi H., et al. Study of the upregulation of the activity of cytochrome P450 3A isoforms by Astragalus injection and Astragalus granules in rats and in cells [J]. Eur J Drug Metab Pharmacokinet,2012,
[148]Malati C. Y., Robertson S. M., Hunt J. D., et al. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants [J]. J Clin Pharmacol,2012,52 (6):932-939.
[149]Li Y., Wang Q., Yao X. Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor-and pregnane X receptor-mediated pathways [J]. Eur J Pharmacol,2010,640 (1-3): 46-54.
[150]Yu C., Ye S., Sun H., et al. PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA[J]. Chem Biol Interact,2009,177 (1):58-64.
[151]董海燕,邵敬伟,王涛,等.四种抗癌中药提取物对大鼠肝CYP3A酶活性及mRNA表达的影响[J].中药材,2008,31(1)：68-71.
[152]Pao L. H., Hu 0. Y., Fan H. Y., et al. Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo[J]. Am J Chin Med,2012,40 (1):57-73.
[153]Liu Y., Zhang J. W., Li W., et al. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes [J]. Toxicol Sci,2006,91 (2):356-364.
[154]He N.,Edeki T. The inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes[J]. Am J Ther,2004,11 (3):206-212.
[155]A unified nomenclature system for the nuclear receptor superfamily[J]. Cell,1999, 97 (2):161-163.
[156]胡承,贾伟平.PPAR δ与脂代谢及胰岛素抵抗[J].国际内分泌代谢杂志,2006,26(6)：385-387.
[157]Higashiyama H., Billin A. N., Okamoto Y., et al. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray[J]. Histochem Cell Biol,2007,127 (5):485-494.
[158]Bojic L. A., Sawyez C. G., Telford D. E., et al. Activation of peroxisome proliferator-activated receptor delta inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein[J]. Arterioscler Thromb Vasc Biol,2012,32 (12):2919-2928.
[159]Brown J. D., Oligino E., Rader D. J., et al. VLDL hydrolysis by hepatic lipase regulates PPARdelta transcriptional responses[J]. PLoS One,2011,6 (7):e21209.
[160]Benetti E., Patel N. S..Collino M. The role of PPARbeta/delta in the management of metabolic syndrome and its associated cardiovascular complications [J]. Endocr Metab Immune Disord Drug Targets,2011,11 (4):273-284.
[161]Krogsdam A. M., Nielsen C. A., Neve S., et al. Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation[J]. Biochem J,2002,363 (Pt 1):157-165.
[162]Shi Y., Hon M., Evans R. M. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling [J]. Proc Natl Acad Sci U S A,2002,99 (5):2613-2618.
[163]Ruan X., Zheng F., Guan Y. PPARs and the kidney in metabolic syndrome[J]. Am J Physiol Renal Physiol,2008,294 (5):F1032-1047.
[164]Abdelrahman M., Sivarajah A., Thiemermann C. Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock [J]. Card iovasc Res,2005, 65 (4):772-781.
[165]Diradourian C., Girard J., Pegorier J. P. Phosphorylation of PPARs:from molecular characterization to physiological relevance[J]. Biochimie,2005,87 (1):33-38.
[166]Moraes L. A., Swales K. E., Wray J. A., et al. Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets [J]. Blood,2007,109 (9): 3741-3744.
[167]Gao L., Tao Y., Zhang L, et al. Vitamin D receptor genetic polymorphisms and tuberculosis:updated systematic review and meta-analysis[J]. Int J Tuberc Lung Dis,2010, 14 (1):15-23.
[168]Wu-Wong J. R. Potential for vitamin D receptor,agonists in the treatment of cardiovascular disease[J]. Br J Pharmacol,2009,158 (2):395-412.
[169]Sertznig P., Seifert M., Tilgen W., et al. Activation of vitamin D receptor (VDR)-and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines[J]. Dermatoendocrinol,2009,1 (4):232-238.
[170]McHowat J.,Creer M. H. Catalytic features, regulation and function of myocardial phospholipase A2[J]. Curr Med Chem Cardiovasc Hematol Agents,2004,2 (3):209-218.
[171]Caslake M. J., Packard C. J., Suckling K. E., et al. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase:a potential new risk factor for coronary artery disease[J]. Atherosclerosis,2000,150 (2):413-419.
[172]Wang Q., Hao Y., Mo X., et al. PLA2G7 gene polymorphisms and coronary heart disease risk:a meta-analysis[J]. Thromb Res,2010,126 (6):498-503.
[173]Packard C. J., O'Reilly D. S., Caslake M. J., et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group[J]. N Engl J Med,2000,343 (16):1148-1155.
[174]Jenkins C. M., Cedars A., Gross R. W. Eicosanoid signalling pathways in the heart [J]. Cardiovasc Res,2009,82 (2):240-249.
[175]Michalski L., Kleniewska P., Piechota-Polanczyk A., et al. The role of endothelin-1 and its receptor blockers on the liver function[J]. Gen Physiol Biophys,2012,31 (4): 383-388.
[176]Pernow J., Shemyakin A., Bohm F. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus[J]. Life Sci,2012,91 (13-14):507-516.
[177]Simeone S. M., Li M. W., Paradis P., et al. Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium[J]. Physiol Genomics,2011, 43 (3):148-160.
[178]Takakuwa T., Endo S., Nakae H., et al. Relationship between plasma levels of type Ⅱ phospholipase A2, PAF acetylhydrolase, endothelin-1, and thrombomodulin in patients with infected burns[J]. Res Commun Mol Pathol Pharmacol,1994,86 (3):335-340.
[179]Yousufzai S. Y., Abdel-latif A. A. Endothelin-1 stimulates the release of arachidonic acid and prostaglandins in cultured human ciliary muscle cells:activation of phospholipase A2[J]. Exp Eye Res,1997,65 (1):73-81.
[180]Romanelli F., Fillo S., Isidori A., et al. Stimulatory action of endothelin-1 on rat Leydig cells:involvement of endothelin-A subtype receptor and phospholipase A2-arachidonate metabolism system[J]. Life Sci,1997,61 (5):557-566.
[181]Kieffer B. L. Opioids:first lessons from knockout mice[J]. Trends Pharmacol Sci, 1999,20 (1):19-26.
[182]Matthes H. W., Maldonado R., Simonin F., et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene[J]. Nature,1996,383 (6603):819-823.
[183]Simon E. J. Subunit structure and purification of opioid receptors[J]. J Recept Res,1987,7 (1-4):105-132.
[184]吴符火,刘雪酶,贾铷.丹七胶囊的药效学研究[J].中国中药杂志,2005,30(23)：1869-1873.
[185]毛春芹,陆兔林,邱鲁婴.三棱不同炮制品总黄酮镇痛作用研究[J].南京中医药大学学报(自然科学版),2001,17(5)：299-300.
[186]鲁汉兰,彭智聪,刘勇,等.莪术炮制后对止痛及活血化瘀作用的影响[J].中成药,2000,22(2)：27-29.
[187]王一菱, 陈迪,吴景兰.三七总皂甙抗炎和镇痛作用及其机理探讨[J].中国中西医结合杂志,1994,14(1)：35-36,35-36.
[188]Li Z., Li L., Zielke H. R., et al. Increased expression of 72-kd type IV collagenase (MMP-2) inhuman aortic atherosclerotic lesions[J]. Am J Pathol,1996,148 (1):121-128.
[189]Alp E., Menevse S., Tulmac M., et al. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction[J]. Genet Test Mol Biomarkers,2011,15 (4):193-202.
[190]Pasterkamp G., Schoneveld A. H., Hijnen D. J., et al. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1,2 and 9 in the human coronary artery[J]. Atherosclerosis,2000,150 (2):245-253.
[191]Fert-Bober J., Leon H., Sawicka J., et al. Inhibiting matrix metalloproteinase-2 reduces protein release into coronary effluent from isolated rat hearts during ischemia-reperfusion[J]. Basic Res Cardiol,2008,103 (5):431-443.
[192]Dhillon O. S., Khan S. Q., Narayan H. K., et al. Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome[J]. Clin Sci (Lond),2010,118 (4): 249-257.
[193]Clark A. W., Krekoski C. A., Bou S. S., et al. Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia[J]. Neurosci Lett, 1997,238 (1-2):53-56.
[194]王凤,金笑平.基质金属蛋白酶2及其基因多态性与动脉粥样硬化的关系[J].医学综述,2010,16(20)：3041-3043.
[195]Grote K., Flach I., Luchtefeld M., et al. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species[J]. Circ Res,2003,92 (11):e80-86.
[196]Dai Y., Bae K., Siemann D. W. Impact of hypoxia on the metastatic potential of human prostate cancer cells[J]. Int J Radiat Oncol Biol Phys,2011,81 (2):521-528.
[197]Lim C. S., Qiao X., Reslan 0. M., et al. Prolonged mechanical stretch is associated with upregulation of hypoxia-inducible factors and reduced contraction in rat inferior vena cava[J]. J Vasc Surg,2011,53 (3):764-773.
[198]Jovanovic M., Stefanoska I., Radojcic L., et al. Interleukin-8 (CXCL8) stimulates trophoblast cell migration and invasion by increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins alpha5 and betal[J]. Reproduction,2010,139 (4):789-798.
[199]Mulayim N., Savlu A., Guzeloglu-Kayisli 0., et al. Regulation of endometrial stromal cell matrix metalloproteinase activity and invasiveness by interleukin-8[J]. Fertil Steril,2004,81 Suppl 1904-911.
[200]许晓乐,季晖,谷舒怡,等.黄芪甲苷对小鼠实验性心室重构及基质金属蛋白酶表达的影响[J].中国药科大学学报,2010,41(1)：70-75.
[201]殷春嫒.黄芪对兔动脉粥样硬化模型基质金属蛋白酶-2,9的抑制作用.硕士论文.吉林大学,27,2009.
[202]石耀辉.人参皂苷Rb3对大鼠心肌缺血再灌注损伤的保护作用及其对大鼠心肌梗死不同阶段基质金属蛋白酶的影响.博士论文.吉林大学,77,2012.
[203]Curry S. Lessons from the crystallographic analysis of small molecule binding to human serum albumin[J]. Drug Metab Pharmacokinet,2009,24 (4):342-357.
[204]Tamion F. [Albumin in sepsis][J]. Ann Fr Anesth Reanim,2010,29 (9):629-634.
[205]Donadio C., Tognotti D., Donadio E. Albumin modification and fragmentation in renal disease[J]. Clin Chim Acta,2012,413 (3-4):391-395.
[206]Roche M., Rondeau P., Singh N. R., et al. The antioxidant properties of serum albumin[J]. FEBS Lett,2008,582 (13):1783-1787.
[207]杜卫东,叶再元,徐旭军.人参皂甙对腹腔感染大鼠血清白蛋白的影响[J].浙江中医学院学报,2003,(2)：58-59.
[208]Wang M., Wang Y., Weil B., et al. Estrogen receptor beta mediates increased activation of PI3K/Akt signaling and improved myocardial function in female hearts following acute ischemia[J]. Am J Physiol Regul Integr Comp Physiol,2009,296 (4): R972-978.
[209]Haynes M. P., Li L., Sinha D., et al. Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen[J]. J Biol Chem,2003,278 (4):2118-2123.
[210]Martignoni M., Groothuis G. M., de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction[J]. Expert Opin Drug Metab Toxicol,2006,2 (6):875-894.
[211]Imai J., Ieiri I., Mamiya K., et al. Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients:genetic analysis of the CYP2C9 locus[J]. Pharmacogenetics,2000,10 (1):85-89.
[212]Hirota T., Eguchi S., Ieiri I. Impact of Genetic Polymorphisms in CYP2C9 and CYP2C19 on the Pharmacokinetics of Clinically Used Drugs [J]. Drug Metab Pharmacokinet,2013,28 (1):28-37.
[213]Wilkinson G. R., Guengerich F. P., Branch R. A. Genetic polymorphism of S-mephenytoin hydroxylation[J]. Pharmacol Ther,1989,43 (1):53-76.
[214]Andersson T., Regardh C. G., Lou Y. C., et al. Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects[J]. Pharmacogenetics,1992,2 (1):25-31.
[215]Sindrup S. H., Brosen K., Hansen M. G., et al. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms [J]. Ther Drug Monit, 1993,15 (1):11-17.
[216]Bertilsson L., Henthorn T. K., Sanz E., et al. Importance of genetic factors in the regulation of diazepam metabolism:relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype[J]. Clin Pharmacol Ther,1989,45 (4):348-355.
[217]Shu Y., Wang L. S., Xiao W. M., et al. Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone[J]. Acta Pharmacol Sin,2000,21 (8):753-758.
[218]何楠,周宏灏CYP2C19遗传多态性的研究进展[J].生理科学进展,2003,34(2)：171-174.
[219]毕惠嫦,和凡,温莹莹,等.丹参酮II_A在大鼠肝微粒体酶中的代谢动力学[J].中草药,2007,38(6)：882-886.
[220]赵慧娟.中药对大鼠CYP2D6、CYP1A2和CYP2C19的抑制作用.硕士论文.郑州大学,38.2009.
[221]马萍,胡荣,王小英,等.中药人参治疗糖尿病的研究进展[J].湖北中医药大学学报,2013,15(1)：63-65.
[222]杨晓,蒋丽平,王书.黄芪多糖对高脂血症大鼠血脂、免疫功能及氧化应激指标的影响[J].现代中药研究与实践,2012,26(5)：37-40.
[223]贡云华,蒋家雄,李泽,等.三七皂甙C1对四氧嘧啶糖尿病小鼠的降血糖作用[J].药学学报,1991,26(2)：81-85.
[1]衷敬柏,董绍英,王阶,等.2689例冠心病心绞痛证候要素的文献统计分析[J].中国中医药信息杂志,2006,13(5)：100-101.
[2]何庆勇,王阶,张允岭,等.冠心病介入术后再狭窄危险因素及中医证候要素分析[J].北京中医药大学学报,2008,31(8)：569-572.
[3]张秋雁,邓冰湘.冠心病心绞痛临床中医证型分布的回顾性分析[J].中医研究,2005,18(11)：23-24.
[4]陈世宏,叶耘,尚正录,等.黄芪保心汤对缺血心肌心功能及心肌细胞超微结构的影响[J].中华中医药学刊,2008,26(2)：376-378.
[5]姜浩,农一兵,林谦.益气活血药对心梗后心功能不全大鼠心肌细胞RYR2、SERCA2a及PLBmRNA表达的影响[J].中华中医药杂志,2011,26(9)：1957-1960.
[6]尹慧秋,张继东,乔云,等.舒脉胶囊对心肌缺血大鼠心肌细胞凋亡的影响[J].山东大学学报(医学版),2007,179(7)：739-742.
[7]李敏,王硕仁,赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响[J].中西医结合心脑血管病杂志,2005,3(1)：33-35.
[8]杨建飞,杨颖,孙静,等.人参黄芪含药血清对人脐静脉内皮细胞活性的影响[J].中医药信息,2012,29(2)：21-23.
[9]励石寒,卢慧勤,陈孝.参芪培元口服液保护急性心肌缺血损伤的机制研究[J].中国药师,2004,7(10)：747-749.
[10]赵贵起,周爱民,李秀军,等.补阳还五汤对高脂血症大鼠血流变及血清一氧化氮的影响[J].河北中医,2009,31(6)：911-913.
[11]宫爱华,孙素琴,荣文平.心痛滴剂治疗冠心病心绞痛的实验研究[J].辽宁中医杂志,2004,31(5)：434-435.
[12]章怡祎,刘萍,高虹,等.冠心康对脂质损伤的人血管内皮细胞保护机制的研究[J].中医药学刊,2005,23(8)：1418-1419.
[13]侯霄雷,李白翎,赵雷,等.血府逐瘀胶囊对急性心肌梗死再灌注后心肌及内皮素-1、一氧化氮／一氧化氮合酶体系影响的实验研究[J].中西医结合学报,2008,6(4)：381-386.
[14]韩旭,李七一,夏卫军,等.通心络胶囊对载脂蛋白E基因敲除小鼠冠状动脉粥样硬化的影响及其机理研究[J].中国中医药信息杂志,2011,18(2)：37-40.
[15]吴爱明,张冬梅,娄利霞,等.生脉注射液联合血塞通注射液对心肌梗死大鼠室颤阈值和心肌连接蛋白43表达的影响[J].中西医结合学报,2011,9(7)：775-782.
[16]张会超,韩丽华,王振涛,等.益气活血方对心梗后左室重构大鼠心肌基质金属蛋白酶-2、转化生长因子-β_1的影响[J].中成药,2010,32(11)：1871-1874.
[17]姜大伟,赵学忠,于晓风,等.西洋参茎叶三醇组皂苷对大鼠压力超负荷性心室重构的保护作用[J].中华老年医学杂志,2011,11(30)：953-957.
[18]韩冬,于晓风,曲绍春,等.人参皂苷Rb_3对大鼠实验性心室重构的影响及其机制[J].吉林大学学报(医学版),2010,36(6)：1047-105 I+1993.
[19]卢应,董均树,刘娅,等.西洋参叶20S-原人参二醇组皂苷对大鼠实验性心室重构的影响[J].中草药,2009,40(11)：1785-1787.
[20]张志毅,梅轶芳,赵彦萍,等.益气活血化痰法中药对泡沫细胞基质金属蛋白酶1/2mRNA表达的影响[J].中国中西医结合急救杂志,2005,12(4)：238-241.
[21]刘月玲,朱秋玲.参七粉对动脉粥样硬化家兔血脂代谢及血管内皮功能的影响[J].中国医药导报,2012,9(6)：26-28.
[22]肖纯,孙明,金益强,等.通脉颗粒对兔动脉粥样硬化模型血脂水平及主动脉和冠状动脉病变的影响[J].中国动脉硬化杂志,2005,13(6)：705-708.
[23]姜丽红,陈立红.益气活血方对实验性心肌梗死大鼠心肌梗死面积及VEGF、bFGF、Ⅷ表达量的影响[J].世界中西医结合杂志,2011,6(12)：1067-1070.
[24]王振涛,王硕仁,赵明镜,等.活血、益气方药对心梗后左心衰大鼠血TNF和血小板聚集影响的对比研究[J].中国中医药信息杂志,2002,9(11)：20-22.
[25]钟超,夏承来.丹参酮II_A对大鼠血管内皮细胞血栓调节蛋白表达的影响[J].中药材,2010,33(3)：425-427.
[26]李响,张愚,马雪涛,等.注射用血栓通对白细胞黏附及相关黏附分子表达影响的体外实验研究[J].中华中医药学刊,2009,27(10)：2200-2202.
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