中医药对血管新生促进或抑制作用的研究进展
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摘要
中医药促进或抑制血管新生在缺血性心脑血管疾病和肿瘤中的应用是目前研究的热点。本文对国内外近5年(2012年-2017年)相关文献进行整理,发现促进血管新生的复方多是益气活血化瘀类,如血府逐瘀汤、当归补血汤、补阳还五汤、桃红四物汤、芪参益气方等,单味中药如川芎、丹参、黄芪、人参、三七、红花、当归等,中药药对如黄芪与当归、川芎与黄芪、当归与赤芍等;其作用机制与血管内皮生长因子(VEGFA、VEGFB)及其受体Flt-1(VEGFR1)、KDR/Flk-1(VEGFR2)、血管生成素(Ang)-1及其受体Tie-2密切相关。而抗血管新生的多是清热燥湿解毒散结的复方(如鳖甲煎丸、复方苦参注射液、西黄丸、六神丸、解毒消癥饮等),单味中药如姜黄、半枝莲、黄芩、雷公藤、蟾酥、蝎毒等居多,其机制多是抑制基质金属蛋白酶(MMPs)的活性,如降低MMP-2、TIMP-1的表达或者抑制VEGF、bFGF等促血管生成因子的表达。通过概述中医药对血管新生促进或抑制的作用,可为今后相关的研究提供更多的思路。
Application of Chinese medicines in promoting or inhibiting angiogenesis in ischemic cardiovascular and cerebrovascular diseases and tumors is always a hot topic of research.In this paper,we analyze the relevant literature at home and abroad in recent 5 years(2012-2017)and find the herb compounds that develop angiogenesis mainly promote circulation of Qi and blood,such as Xuefu Zhuyu Decoction,Danggui Buxue Decoction,Buyang Huanwu Decoction,Taohong Siwu Decoction,and Qishen Yiqi Decoction;single herbs such as Chuanxiong,Salvia,Astragalus,Ginseng,Panax,safflower,and angelica;Chinese medicines in pair such as Astragalus and Angelica,Chuanxiong and Astragalus,Angelica and red peony.The acting mechanism is closely related to VEGFA and VEGFB and their receptors Flt-1(VEGFR1),KDR/Flk-1(VEGFR2),Ang-1 and its receptor Tie-2.Antiangiogenesis medicines are mostly heat and dampness detoxification Sanjie compounds(such as turtle pills,compound bitter ginseng injections,West Huang Wan,Liushen pills,and detoxification and Xiao Zheng drink);single herbs such as turmeric,Scutellaria barbata,Scutellaria,Tripterygium,toad,and scorpion venom.The mechanism is inhibiting the activity of MMPs,such as reducing the expressions of MMP-2 and TIMP-1 or inhibiting the expressions of angiogenic factors such as VEGF and bFGF.By summarizing the role of Chinese medicines in promoting or inhibiting angiogenesis,we hope to provide more ideas for future related research.
Application of Chinese medicines in promoting or inhibiting angiogenesis in ischemic cardiovascular and cerebrovascular diseases and tumors is always a hot topic of research.In this paper,we analyze the relevant literature at home and abroad in recent 5 years(2012-2017)and find the herb compounds that develop angiogenesis mainly promote circulation of Qi and blood,such as Xuefu Zhuyu Decoction,Danggui Buxue Decoction,Buyang Huanwu Decoction,Taohong Siwu Decoction,and Qishen Yiqi Decoction;single herbs such as Chuanxiong,Salvia,Astragalus,Ginseng,Panax,safflower,and angelica;Chinese medicines in pair such as Astragalus and Angelica,Chuanxiong and Astragalus,Angelica and red peony.The acting mechanism is closely related to VEGFA and VEGFB and their receptors Flt-1(VEGFR1),KDR/Flk-1(VEGFR2),Ang-1 and its receptor Tie-2.Antiangiogenesis medicines are mostly heat and dampness detoxification Sanjie compounds(such as turtle pills,compound bitter ginseng injections,West Huang Wan,Liushen pills,and detoxification and Xiao Zheng drink);single herbs such as turmeric,Scutellaria barbata,Scutellaria,Tripterygium,toad,and scorpion venom.The mechanism is inhibiting the activity of MMPs,such as reducing the expressions of MMP-2 and TIMP-1 or inhibiting the expressions of angiogenic factors such as VEGF and bFGF.By summarizing the role of Chinese medicines in promoting or inhibiting angiogenesis,we hope to provide more ideas for future related research.
引文
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[5]王飞龙,韩岚,樊玲,等.桃红四物汤对实验性脑缺血大鼠血清中ET-1,Ang-1,VEGF的影响[J].中国实验方剂学杂志,2017,23(1):101-106.
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[10]方凌燕,刘衍宇,李国达,等.丹参多酚酸盐对大鼠梗死后心肌组织血管新生的影响及机制研究[J].国际心血管病杂志,2015,42(4):256-260.
[11]李军昌,司静文,刘海涛,等.黄芪甲苷Ⅳ对梗死小鼠心肌新生血管成熟及HIF-1α、VEGF蛋白表达的影响[J].心脏杂志,2017,29(3):269-275.
[12]周勇,姚昶,高峰,等.黄芪多糖胶原干预周围组织中核因子κB与血管内皮细胞生长因子表达而促进毛细血管新生[J].中国组织工程研究,2012,16(7):1184-1187.
[13]刘暖,杨雷,毛秉豫,等.黄芪提取物对大鼠心肌梗死后心肌组织血管新生的作用[J].中国实验方剂学杂志,2015,21(19):92-96.
[14]魏英,余丽梅,王钰莹,等.人参总皂苷促进血管新生改善急性心肌梗死大鼠心功能[J].中国药理学通报,2016,32(4):559-564.
[15]陈社带,邹燕,赵伟国,等.三七总皂苷对大鼠缺血心肌血管新生及相关生长因子的影响[J].辽宁医学院学报,2015,36(1):7-9.
[16]邹江,王慷慨,刘曼婷,等.羟基红花黄色素A促血管新生的新机制[J].中国病理生理杂志,2015,31(10):1830.
[17]付卫云,刘暖,杨雷,等.红景天苷促大鼠心肌梗死后心肌组织血管新生的作用[J].中药药理与临床,2015,31(5):30-34.
[18]王玉梅,刘永平,曹凯,等.黄芩茎叶黄酮对慢性脑缺血大鼠脑内NMDA受体和VEGF表达的影响[J].中国病理生理杂志,2012,28(2):353-357.
[19]郭重仪.黄芩苷对脂质过氧化及内皮细胞氧化损伤的保护作用[J].中药材,2012,35(2):288-291.
[20]魏述永.葛根素心血管保护作用及其机制研究进展[J].中国中药杂志,2015,40(12):2278-2284.
[21]李杏芮,陈清,盛华均.白藜芦醇通过介导eNOS表达促进局灶脑缺血/再灌注大鼠脑内血管再生[J].中国组织化学与细胞化学杂志,2016,25(6):506-511.
[22]李悦山,张建龙,薛磊.黄芪与当归对人脐静脉内皮细胞增殖及VEGF表达的影响[J].新疆医科大学学报,2005,28(3):224-227.
[23]杨锋.黄芪、地黄混合提取物促新生血管形成的作用及其机制[J].武汉大学学报(医学版),2014,35(03):370-374.
[24]张大方,韩旭,李玉梅,等.川芎嗪与黄芪甲苷不同浓度配伍对血管新生的影响[J].吉林师范大学学报(自然科学版),2016,37(2):111-114.
[25]文彬,孙海涛,贺松其,等.鳖甲煎丸对HepG2裸鼠移植瘤的抑制作用及瘤体组织中β-catenin、Tbx3表达水平的影响[J].南方医科大学学报,2016,36(2):210-214.
[26]任征远,马杰,王一尧,等.西黄丸对乳腺荷瘤小鼠外周血和肿瘤组织VEGF、MMP9表达的影响[J].中成药,2016,38(2):440-443.
[27]王怡鑫,蒋刚,蔡红,等.复方苦参注射液联合化疗对结直肠癌患者血清血管内皮生长因子的影响[J].现代中西医结合杂志,2016,25(15):1685-1686.
[28]来雷,翟昌林,杨林军,等.复方苦参注射液对肺癌裸鼠移植瘤的抑制作用及其MMP-9、VEGF表达的影响[J].中国中医药科技,2013,20(1):21-22.
[29]司海龙,王立芳,徐振晔,等.肺岩宁颗粒对Lewis肺癌小鼠肿瘤相关巨噬细胞及肿瘤转移的影响[J].上海中医药大学学报,2016,30(3):47-52.
[30]阮善明,沈敏鹤,郑丽萍,等.解毒三根汤对结肠癌相关成纤维细胞VEGF、IL-6的影响及对Caspase信号通路的探讨[J].中华中医药杂志,2014,29(12):3936-3939.
[31]徐步远,潘显阁,陈崇别,等.姜黄素对Lewis肺癌小鼠血管内皮成长因子和endostatin表达的影响[J].中国临床药理学与治疗学,2017,22(2):151-154.
[32]江红,毛小刚.姜黄素对小鼠宫颈癌皮下移植瘤模型外周血和肿瘤组织MMP2、MMP9、VEGF表达的影响[J].临床和实验医学杂志,2016,15(9):832-835.
[33]YANG X,YANG Y,TANG S,et al.Anti-tumor effect of polysaccharides from Scutellaria Barbata D.Don on the 95-D xenograft model via inhibition of the C-Met pathway[J].J Pharmacol Sci,2014,125(3):255-263.
[34]王淑静,董立强,刘欢,等.雷公藤红素对SGC-7901细胞和ECV304细胞增殖及能量代谢的影响[J].中草药,2016,47(21):3854-3860.
[35]宋红群,王宁,张延新.黄芩素对人结肠癌裸鼠移植瘤生长及小鼠血清VEGF,TNF-α水平的影响[J].中国医药科学,2015,5(23):28-30.
[36]TAMAGAWA K,HORIUCHI T,WADA T,et al.Polysaccharide-K(PSK)may suppress surgical stress-induced metastasis in rat colon cancer[J].Langenbecks Arch Surg,2012,397(3):475-480.
[37]ZHU D,WANG S,LAWLESS J,et al.Dose-dependent dual effect of Baicalin and Herb Huang Qin Extract on angiogenesis[J].PLoS One,2016,11(11):e0167125.
[2]高冬,陈文元,林薇,等.血府逐瘀汤促血管新生中VEGF通路的作用研究[J].中国中药杂志,2012,37(17):2622-2625.
[3]许晓玲,蔡飞,林凡,等.血府逐瘀汤促血管新生中EphB4/ephrinB2信号通路的作用研究[J].中国中医基础医学杂志,2016,22(3):362-364.
[4]SHEN J,ZHU Y,YU H.Buyang Huanwu decoction increases angiopoietin-1 expression and promotes angiogenesis and functional outcome after focal cerebral ischemia[J].J Zhejiang Univ Sci B,2014,15(3):272-280.
[5]王飞龙,韩岚,樊玲,等.桃红四物汤对实验性脑缺血大鼠血清中ET-1,Ang-1,VEGF的影响[J].中国实验方剂学杂志,2017,23(1):101-106.
[6]黄斐斐,刘阳,陈洁,等.麝香保心丸通过上调20-HETE调控内皮祖细胞促进心肌梗死大鼠血管新生[J].岭南急诊医学杂志,2016,21(1):4-6.
[7]张腾,张密霞,张艳军.芪参益气滴丸抗血管新生大鼠心肌缺血动态观察及机制探讨[J].中国实验方剂学杂志,2017,23(1):134-139.
[8]马进,甘雨,袁媛,等.川芎赤芍干预脑缺血再灌注大鼠血管新生的实验研究[J].世界中医药,2016,11(6):1060-1062.
[9]卫国,段佳林,殷英,等.丹参素和羟基红花黄色素A促血管新生及抗大鼠心肌梗死作用研究[J].时珍国医国药,2016,27(11):2576-2578.
[10]方凌燕,刘衍宇,李国达,等.丹参多酚酸盐对大鼠梗死后心肌组织血管新生的影响及机制研究[J].国际心血管病杂志,2015,42(4):256-260.
[11]李军昌,司静文,刘海涛,等.黄芪甲苷Ⅳ对梗死小鼠心肌新生血管成熟及HIF-1α、VEGF蛋白表达的影响[J].心脏杂志,2017,29(3):269-275.
[12]周勇,姚昶,高峰,等.黄芪多糖胶原干预周围组织中核因子κB与血管内皮细胞生长因子表达而促进毛细血管新生[J].中国组织工程研究,2012,16(7):1184-1187.
[13]刘暖,杨雷,毛秉豫,等.黄芪提取物对大鼠心肌梗死后心肌组织血管新生的作用[J].中国实验方剂学杂志,2015,21(19):92-96.
[14]魏英,余丽梅,王钰莹,等.人参总皂苷促进血管新生改善急性心肌梗死大鼠心功能[J].中国药理学通报,2016,32(4):559-564.
[15]陈社带,邹燕,赵伟国,等.三七总皂苷对大鼠缺血心肌血管新生及相关生长因子的影响[J].辽宁医学院学报,2015,36(1):7-9.
[16]邹江,王慷慨,刘曼婷,等.羟基红花黄色素A促血管新生的新机制[J].中国病理生理杂志,2015,31(10):1830.
[17]付卫云,刘暖,杨雷,等.红景天苷促大鼠心肌梗死后心肌组织血管新生的作用[J].中药药理与临床,2015,31(5):30-34.
[18]王玉梅,刘永平,曹凯,等.黄芩茎叶黄酮对慢性脑缺血大鼠脑内NMDA受体和VEGF表达的影响[J].中国病理生理杂志,2012,28(2):353-357.
[19]郭重仪.黄芩苷对脂质过氧化及内皮细胞氧化损伤的保护作用[J].中药材,2012,35(2):288-291.
[20]魏述永.葛根素心血管保护作用及其机制研究进展[J].中国中药杂志,2015,40(12):2278-2284.
[21]李杏芮,陈清,盛华均.白藜芦醇通过介导eNOS表达促进局灶脑缺血/再灌注大鼠脑内血管再生[J].中国组织化学与细胞化学杂志,2016,25(6):506-511.
[22]李悦山,张建龙,薛磊.黄芪与当归对人脐静脉内皮细胞增殖及VEGF表达的影响[J].新疆医科大学学报,2005,28(3):224-227.
[23]杨锋.黄芪、地黄混合提取物促新生血管形成的作用及其机制[J].武汉大学学报(医学版),2014,35(03):370-374.
[24]张大方,韩旭,李玉梅,等.川芎嗪与黄芪甲苷不同浓度配伍对血管新生的影响[J].吉林师范大学学报(自然科学版),2016,37(2):111-114.
[25]文彬,孙海涛,贺松其,等.鳖甲煎丸对HepG2裸鼠移植瘤的抑制作用及瘤体组织中β-catenin、Tbx3表达水平的影响[J].南方医科大学学报,2016,36(2):210-214.
[26]任征远,马杰,王一尧,等.西黄丸对乳腺荷瘤小鼠外周血和肿瘤组织VEGF、MMP9表达的影响[J].中成药,2016,38(2):440-443.
[27]王怡鑫,蒋刚,蔡红,等.复方苦参注射液联合化疗对结直肠癌患者血清血管内皮生长因子的影响[J].现代中西医结合杂志,2016,25(15):1685-1686.
[28]来雷,翟昌林,杨林军,等.复方苦参注射液对肺癌裸鼠移植瘤的抑制作用及其MMP-9、VEGF表达的影响[J].中国中医药科技,2013,20(1):21-22.
[29]司海龙,王立芳,徐振晔,等.肺岩宁颗粒对Lewis肺癌小鼠肿瘤相关巨噬细胞及肿瘤转移的影响[J].上海中医药大学学报,2016,30(3):47-52.
[30]阮善明,沈敏鹤,郑丽萍,等.解毒三根汤对结肠癌相关成纤维细胞VEGF、IL-6的影响及对Caspase信号通路的探讨[J].中华中医药杂志,2014,29(12):3936-3939.
[31]徐步远,潘显阁,陈崇别,等.姜黄素对Lewis肺癌小鼠血管内皮成长因子和endostatin表达的影响[J].中国临床药理学与治疗学,2017,22(2):151-154.
[32]江红,毛小刚.姜黄素对小鼠宫颈癌皮下移植瘤模型外周血和肿瘤组织MMP2、MMP9、VEGF表达的影响[J].临床和实验医学杂志,2016,15(9):832-835.
[33]YANG X,YANG Y,TANG S,et al.Anti-tumor effect of polysaccharides from Scutellaria Barbata D.Don on the 95-D xenograft model via inhibition of the C-Met pathway[J].J Pharmacol Sci,2014,125(3):255-263.
[34]王淑静,董立强,刘欢,等.雷公藤红素对SGC-7901细胞和ECV304细胞增殖及能量代谢的影响[J].中草药,2016,47(21):3854-3860.
[35]宋红群,王宁,张延新.黄芩素对人结肠癌裸鼠移植瘤生长及小鼠血清VEGF,TNF-α水平的影响[J].中国医药科学,2015,5(23):28-30.
[36]TAMAGAWA K,HORIUCHI T,WADA T,et al.Polysaccharide-K(PSK)may suppress surgical stress-induced metastasis in rat colon cancer[J].Langenbecks Arch Surg,2012,397(3):475-480.
[37]ZHU D,WANG S,LAWLESS J,et al.Dose-dependent dual effect of Baicalin and Herb Huang Qin Extract on angiogenesis[J].PLoS One,2016,11(11):e0167125.