中药促进脑缺血血管生成研究进展
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摘要
单味药及其有效成分、中药复方及中成药对血管的促进、抑制作用为目前研究热点,但中药对脑缺血后促进血管生成的作用及机制相关研究尚未深入。本文对中药促进脑血管生成的中医理论、体外研究、在体研究进行综述,并对通过Notch和Wnt信号通路调控血管生成的机制研究进行重点阐述,为药理作用机制研究及新药研发提供参考。
The promotion or inhibition of blood vessels by TCM, active ingredients of TCM, TCM compounds, and Chinese patent drugs is currently a research hotspot, with relatively abundant research. However, the study of the role and profound mechanism of TCM on angiogenesis after cerebral ischemia is relatively rare. Therefore, this article reviewed theories, in vitro studies and in vivo studies on the promotion of cerebral angiogenesis by TCM, and summarized the studies on TCM regulation of angiogenesis through Notch and Wnt signaling pathway mechanisms, with a purpose to provide references for resarch on related mechanisms and development of new deugs.
The promotion or inhibition of blood vessels by TCM, active ingredients of TCM, TCM compounds, and Chinese patent drugs is currently a research hotspot, with relatively abundant research. However, the study of the role and profound mechanism of TCM on angiogenesis after cerebral ischemia is relatively rare. Therefore, this article reviewed theories, in vitro studies and in vivo studies on the promotion of cerebral angiogenesis by TCM, and summarized the studies on TCM regulation of angiogenesis through Notch and Wnt signaling pathway mechanisms, with a purpose to provide references for resarch on related mechanisms and development of new deugs.
引文
[1]TITOV B V,MATVEEVA N A,MARTYNOV M Y,et al.Ischemic stroke as a complex polygenic disease[J].Molecular Biology,2015,49(2):195-216.
[2]涂雪松.缺血性脑卒中的流行病学研究[J].中国临床神经科学,2016,24(5):594-599.
[3]WANG S,OLSON E N.Angiomi Rs-key regulators of angiogenesis[J].Current Opinion in Genetics&Development,2009,19(3):205-211.
[4]HILLMEISTER P,GATZKE N,DüLSNER A,et al.Arteriogenesis is modulated by bradykinin receptor signaling[J].Circulation Research,2011,109(5):524-533.
[5]殷沈华,唐德才.益气活血类中药对血管生成影响的研究[J].时珍国医国药,2013,24(1):43-44.
[6]刘小雨,王行宽.促血管新生的中医药治疗现状[J].中国组织工程研究与临床康复,2007,11(10):1918-1922.
[7]明康文,胡丽竹.益气活血法对急性脑梗死大鼠侧支循环重建影响[J].辽宁中医药大学学报,2016,18(4):17-19.
[8]王蕾,吴志奎,张树成,等.补肾生血中药血管生成活性整体效应的初步探讨[J].中医杂志,2001,42(11):683-685.
[9]马进,甘雨,袁媛,等.川芎赤芍对脑缺血大鼠血管生成素及低氧诱导因子表达的影响[J].中国医药导报,2016,13(17):8-11.
[10]祝慧凤,万东,周佳丽,等.梓醇促局灶性脑缺血大鼠血管新生观察[J].中国中药杂志,2010,35(2):232-236.
[11]王德健,李巧云,徐世军,等.人参皂苷Rg1对新生鼠HIBD后血管再生的影响[J].四川大学学报(医学版),2011,42(4):503-507.
[12]曽联婷,史明,惠娟,等.人参皂甙Rd通过PI3K/AKT/m TOR/Hif-1α通路促进成年大鼠缺血性脑卒中后的血管发生[J].神经解剖学杂志,2015,31(6):686-692.
[13]刘婷婷,孙芳玲,程华,等.莫诺苷对局灶性脑缺血再灌注大鼠血管生成素1及其受体Tie-2的影响[J].中国康复理论与实践,2015,21(1):9-11.
[14]佘颜,王宇红,邵乐,等.补阳还五汤精简方对大鼠脑缺血后血管新生及Nrf2/HO-1信号途径的影响[J].中国药理学通报,2016,32(1):123-128.
[15]HOU Y C,LU C K,WANG Y H,et al.Unique mechanisms of sheng yu decoction(sheng yu tang)on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis[J].Journal of Traditional&Complementary Medicine,2013,3(4):240.
[16]刘轲,李建生,杨歆科,等.脑脉通对老龄大鼠脑缺血/再灌注微血管生成及Flk-1表达的影响[J].北京中医药大学学报,2011,34(1):42-47.
[17]覃仁安,张超群,余小平,等.复方丹参片对急性脑缺血大鼠药理作用的探讨[J].中西医结合心脑血管病杂志,2011,9(9):1092-1094.
[18]何前松,杨红云,胡利民,等.心脑舒通对大鼠脑缺血再灌注损伤缺血周边区微血管新生及Ang/Tie系统表达的影响[J].中国老年学杂志,2015,35(12):3203-3206.
[19]马英姿,刘希伟,潘彦舒,等.通心络超微粉对急性脑梗死大鼠脑微血管的影响[J].中国中医药信息杂志,2014,21(5):61-64.
[20]姚昶,高卫卫,薛涛.黄芪、脉络宁注射液载入修饰胶原对鸡胚尿囊膜血管新生的协同促进作用[J].中国组织工程研究,2010,14(34):6342-6346.
[21]李卫红,王东坡,李兴广,等.通络救脑注射液及其有效成分对拟缺血损伤人脑微血管内皮细胞的保护作用[J].安徽中医药大学学报,2011,30(6):42-46.
[22]林久茂,赵锦燕,林明和,等.芎芍胶囊含药血清对人脐静脉内皮细胞增殖的影响[J].中西医结合心脑血管病杂志,2009,7(1):58-60.
[23]ZHANG P,YAN X,CHEN Y,et al.Notch signaling in blood vessels:from morphogenesis to homeostasis[J].Science China Life Sciences,2014,57(8):774-780.
[24]CRISTOFARO B,SHI Y,FARIA M,et al.Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models[J].Development,2013,140(8):1720-1729.
[25]文丽梅,杨洪军,马超英,等.Wingless/Wnt信号与缺血性脑中风中神经血管单元相关的研究进展[J].中国药理学通报,2013,29(7):903-907.
[26]陈海丽,顾娇阳,张文静,等.经典Wnt信号通路在大鼠脑缺血后血管新生中的作用[J].山东大学学报(医学版),2015,53(4):31-36.
[27]宋祯彦,周瑜,王珊珊,等.中药脑泰方对大鼠脑缺血后VEGF和Angiopoietins表达的实验研究[J].湖南中医药大学学报,2016,36(1):19-22.
[28]ZHU H,HE J,YE L,et al.Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury[J].Toxicol Appl Pharmacol,2015,288(3):313-321.
[29]XU Y,ZHANG G,KANG Z,et al.Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2axis and the Wnt/β-catenin pathway[J].Archives of Pharmacal Research,2016,39(1):133-142.
[30]陈娉婷,周小青,周德生,等.中药对神经干细胞增殖分化相关信号通路调控的研究进展[J].中药新药与临床药理,2015,26(6):859-863.
[2]涂雪松.缺血性脑卒中的流行病学研究[J].中国临床神经科学,2016,24(5):594-599.
[3]WANG S,OLSON E N.Angiomi Rs-key regulators of angiogenesis[J].Current Opinion in Genetics&Development,2009,19(3):205-211.
[4]HILLMEISTER P,GATZKE N,DüLSNER A,et al.Arteriogenesis is modulated by bradykinin receptor signaling[J].Circulation Research,2011,109(5):524-533.
[5]殷沈华,唐德才.益气活血类中药对血管生成影响的研究[J].时珍国医国药,2013,24(1):43-44.
[6]刘小雨,王行宽.促血管新生的中医药治疗现状[J].中国组织工程研究与临床康复,2007,11(10):1918-1922.
[7]明康文,胡丽竹.益气活血法对急性脑梗死大鼠侧支循环重建影响[J].辽宁中医药大学学报,2016,18(4):17-19.
[8]王蕾,吴志奎,张树成,等.补肾生血中药血管生成活性整体效应的初步探讨[J].中医杂志,2001,42(11):683-685.
[9]马进,甘雨,袁媛,等.川芎赤芍对脑缺血大鼠血管生成素及低氧诱导因子表达的影响[J].中国医药导报,2016,13(17):8-11.
[10]祝慧凤,万东,周佳丽,等.梓醇促局灶性脑缺血大鼠血管新生观察[J].中国中药杂志,2010,35(2):232-236.
[11]王德健,李巧云,徐世军,等.人参皂苷Rg1对新生鼠HIBD后血管再生的影响[J].四川大学学报(医学版),2011,42(4):503-507.
[12]曽联婷,史明,惠娟,等.人参皂甙Rd通过PI3K/AKT/m TOR/Hif-1α通路促进成年大鼠缺血性脑卒中后的血管发生[J].神经解剖学杂志,2015,31(6):686-692.
[13]刘婷婷,孙芳玲,程华,等.莫诺苷对局灶性脑缺血再灌注大鼠血管生成素1及其受体Tie-2的影响[J].中国康复理论与实践,2015,21(1):9-11.
[14]佘颜,王宇红,邵乐,等.补阳还五汤精简方对大鼠脑缺血后血管新生及Nrf2/HO-1信号途径的影响[J].中国药理学通报,2016,32(1):123-128.
[15]HOU Y C,LU C K,WANG Y H,et al.Unique mechanisms of sheng yu decoction(sheng yu tang)on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis[J].Journal of Traditional&Complementary Medicine,2013,3(4):240.
[16]刘轲,李建生,杨歆科,等.脑脉通对老龄大鼠脑缺血/再灌注微血管生成及Flk-1表达的影响[J].北京中医药大学学报,2011,34(1):42-47.
[17]覃仁安,张超群,余小平,等.复方丹参片对急性脑缺血大鼠药理作用的探讨[J].中西医结合心脑血管病杂志,2011,9(9):1092-1094.
[18]何前松,杨红云,胡利民,等.心脑舒通对大鼠脑缺血再灌注损伤缺血周边区微血管新生及Ang/Tie系统表达的影响[J].中国老年学杂志,2015,35(12):3203-3206.
[19]马英姿,刘希伟,潘彦舒,等.通心络超微粉对急性脑梗死大鼠脑微血管的影响[J].中国中医药信息杂志,2014,21(5):61-64.
[20]姚昶,高卫卫,薛涛.黄芪、脉络宁注射液载入修饰胶原对鸡胚尿囊膜血管新生的协同促进作用[J].中国组织工程研究,2010,14(34):6342-6346.
[21]李卫红,王东坡,李兴广,等.通络救脑注射液及其有效成分对拟缺血损伤人脑微血管内皮细胞的保护作用[J].安徽中医药大学学报,2011,30(6):42-46.
[22]林久茂,赵锦燕,林明和,等.芎芍胶囊含药血清对人脐静脉内皮细胞增殖的影响[J].中西医结合心脑血管病杂志,2009,7(1):58-60.
[23]ZHANG P,YAN X,CHEN Y,et al.Notch signaling in blood vessels:from morphogenesis to homeostasis[J].Science China Life Sciences,2014,57(8):774-780.
[24]CRISTOFARO B,SHI Y,FARIA M,et al.Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models[J].Development,2013,140(8):1720-1729.
[25]文丽梅,杨洪军,马超英,等.Wingless/Wnt信号与缺血性脑中风中神经血管单元相关的研究进展[J].中国药理学通报,2013,29(7):903-907.
[26]陈海丽,顾娇阳,张文静,等.经典Wnt信号通路在大鼠脑缺血后血管新生中的作用[J].山东大学学报(医学版),2015,53(4):31-36.
[27]宋祯彦,周瑜,王珊珊,等.中药脑泰方对大鼠脑缺血后VEGF和Angiopoietins表达的实验研究[J].湖南中医药大学学报,2016,36(1):19-22.
[28]ZHU H,HE J,YE L,et al.Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury[J].Toxicol Appl Pharmacol,2015,288(3):313-321.
[29]XU Y,ZHANG G,KANG Z,et al.Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2axis and the Wnt/β-catenin pathway[J].Archives of Pharmacal Research,2016,39(1):133-142.
[30]陈娉婷,周小青,周德生,等.中药对神经干细胞增殖分化相关信号通路调控的研究进展[J].中药新药与临床药理,2015,26(6):859-863.