脑缺血血管再生及中医药干预研究
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摘要
血管再生是近年来脑缺血研究中的热点问题,损伤部位的血管新生和血流增加是改善脑缺血损伤和促进神经修复的关键环节之一。脑缺血后血管再生的影响因素及其调控机制较为复杂,探索能有效促进脑缺血后血管再生影响因子,对于探讨血管再生的机制和寻求药物治疗靶点,显得尤为重要。中医药对脑缺血的防治取得一定疗效,加强中医药促进脑缺血后血管再生研究,有助于进一步提高中医药临床疗效和加强中医药新技术方法开发利用。
Angiogenesis is a hot topic in the study of cerebral ischemia in recent years. Angiogenesis and increased blood flow at the site of injury are one of the key links to improve cerebral ischemic injury and promote nerve repair.The factors influencing angiogenesis after cerebral ischemia and its regulatory mechanisms are complex. Exploring the factors that can effectively promote vascular regeneration after cerebral ischemia is particularly important for exploring the mechanism of angiogenesis and seeking drug treatment targets. Chinese medicine has achieved certain effects on the prevention and treatment of cerebral ischemia. Strengthening the study of blood vessel regeneration after cerebral ischemia by Chinese medicine will help to further improve the clinical efficacy of traditional Chinese medicine and strengthening the development and utilization of new methods of traditional Chinese medicine.
Angiogenesis is a hot topic in the study of cerebral ischemia in recent years. Angiogenesis and increased blood flow at the site of injury are one of the key links to improve cerebral ischemic injury and promote nerve repair.The factors influencing angiogenesis after cerebral ischemia and its regulatory mechanisms are complex. Exploring the factors that can effectively promote vascular regeneration after cerebral ischemia is particularly important for exploring the mechanism of angiogenesis and seeking drug treatment targets. Chinese medicine has achieved certain effects on the prevention and treatment of cerebral ischemia. Strengthening the study of blood vessel regeneration after cerebral ischemia by Chinese medicine will help to further improve the clinical efficacy of traditional Chinese medicine and strengthening the development and utilization of new methods of traditional Chinese medicine.
引文
[1]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.
[2]苟芸,黄国伟,赵亚倩,等.同型半胱氨酸对大鼠局灶性脑缺血后血管再生的影响[J].天津医药,2016,44(1):5.
[3]郭建文,李俊雅,黄燕.调节“脑中血海”法联合骨髓间充质干细胞移植对大鼠缺血脑组织血管再生的影响[J].中西医结合学报,2009,7(8):763-768.
[4]惠娟,韩军良.脑缺血损伤后血管再生的研究进展[J].国际神经病学神经外科学杂志,2015,42(2):193.
[5]徐晓明,尤艳利,周爽.针刺促脑缺血后血管新生的研究进展[J].中华中医药学刊,2014,32(1):63.
[6]Trevor DC,Amanda RJ,Ethan CB,et al.Vascular endothelial growth factor:Therapeutic possibilities and challenges for the treatment of ischemia[J].Cytokine,2015,71(2):385-392.
[7]Ju R,Wen Y,Gou R,et al.The experimental therapy on brain ischemia by improvement of local angiogenesis with tissue engineering in themouse[J].Cell Transplant,2014,23(Sup-pl1):83-95.
[8]Zhu Y,Lee C,Shen F,et al.Angiopoietin-2 facilitates vascular endothelial growth factor-induced angiogenesis in the mature mouse brain[J].Stroke,2005,36(7):1533-1537.
[9]Murakami M,Nguyen LT,Zhuang ZW,et al.The FGF sys-tem has a key role in regulating vascular integrity[J].J Clin In-vest,2008,118(10):3355-3366.
[10]周盛年,姜维.浅谈缺血性卒中二级预防[J].中国现代神经疾病杂,2015,15(3):171-176.
[11]凌莉,张素平,吉章阁,等.外源性基质细胞衍生因子-1α对大鼠脑梗死后远隔部位细胞增殖和血管再生的影响[J].中国神经精神疾病杂志,2013,39(10):587-591.
[12]马甲,李连标,徐俊,等.血浆同型半胱氨酸与慢性脑缺血的相关性分析[J].现代实用医学,2016,28(4):453.
[13]苗江永,祝春华,王力娜,等.PI3-K/Akt通路在脑缺血治疗中的调控机制研究[J].脑与神经疾病杂志,2013,21(1):45.
[14]Zhang E,Feng X,Liu F,et al.Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein in-duced HIF-1alpha,VEGF,and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells[J].PLoS One,2014,9:e103440.
[15]Caron A,Richard D,Laplante M.The roles of m TOR complexes in lipid metabolism[J].Annu Rev Nutr,2015,35:321-348.
[16]Dodd KM,Yang J,Shen MH,et al.m TORC1 drives HIF-1alpha and VEGF-Asignalling via multiple mechanisms involving 4E-BP1,S6K1 and STAT3[J].Oncogene,2015,34:2239-2250.
[17]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].山东方大学学报(医学版),2015,53(4):32-35.
[18]Gherghe CM,Duan J,Gong J,et al.Wnt1 is a proangio-genic molecule,enhances human endothelial progenitorfunction,and increases blood flow boischemic limbs in aHGF-dependent manner[J].FASEB J,2011,25(6):1836-1843.
[19]薛金龙,石淑先,孙芳玲,等.Wnt信号通路及相关神经因子对神经再生的影响[J].中国比较医学杂志,2013,23(9):80-6.
[20]Xing XS,Liu F,He ZY.Akt regulatesβ-catenin in a rat model offocal cerebral ischemia-reperfusion injury[J].Molecul Med R eports,2015,11:3122-8.
[21]罗时鹏,余资江,肖朝伦,等.小鼠缺血/再灌注损伤后海马齿状回β-catenin、Cyclin D1的表达变化[J].黔南民族医专学报,2013,26(1):9-13,20.
[22]周强,李朝晖.Notch信号通路在脑缺血的研究进展[J].临床与病理杂志,2015,35(3):452.
[23]Hellstrom M,Phng LK,Hofmann JJ,et al.Dll4 signalling through Notch1regulates formation of tip cells during angiogenesis[J].Nature,2007,445(7129):776-780.
[24]Kwon SM,Eguchi M,Wada M,et al.Specii c Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization[J].Circulation,2008,118(2):157-165.
[25]王荣,李长生.VEGF-Notch/Delta级联信号通路对脑缺血后血管新生的影响[J].山西中医学院学报,2010,11(1):66.
[26]何正光,陈刚,祝慧凤,等.葛根素注射液对大鼠脑缺血/再灌注损伤的保护作用[J].中国药理学通报,2011,27(8):1182.
[27]谭灵莉,崔丹丹,祝慧凤,等.梓醇对脑缺血后神经血管单元构筑的影响[J].中国药理学通报,2014,30(1):47.
[28]曽联婷,史明,惠娟,等.人参皂甙Rd通过PI3K/AKT/mTOR/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.
[29]高海军,白焕焕,雷廷,等.川芎嗪在脑缺血再灌注损伤中的保护作用[J].中国老年学杂志,2015,35(17):5019-5022.
[30]谭辉,王键,尹婷婷,等.脑络欣通方对脑缺血大鼠血管再生及局部脑血流量的影响[J].中国实验方剂学杂志,2015,21(22):21.
[31]俞丽华,王键,陈业农,等.3种中药复方对脑缺血再灌注大鼠脑组织细胞间黏附分子-1和血管内皮生子因子表达的影响[J].中国老年学杂志,2014,34(6):1544.
[32]田兆华,刘柏炎.补阳还五汤对局灶性脑缺血大鼠血管新生的影响[J].中国动脉硬化杂志,2010,18(3):193.
[33]刘柏炎,蔡光先,刘维,等.补阳还五汤对大鼠局灶性脑缺血后血管内皮生长因子及其受体Flk1的影响[J].中草药,2007,38(3):394.
[34]曲铁兵,俞天虹,刘志婷,等.补阳还五汤及其拆方对大鼠脑缺血后神经发生的影响[J].中国中西医结合杂志,2014,34(3):342.
[35]高红莉,王德才,曲晓兰,等.黄芪丹参配伍对局灶性脑缺血再灌注大鼠脑组织VEGF和bFGFmRNA表达的影响[J].中药药理与临床,2013,29(5):95-98.
[36]韩永升,徐银,韩咏竹,等.电针对局灶性脑缺血再灌注大鼠神经血管单元的保护作用[J].针刺研究,2013,38(3):173.
[37]马璟曦,罗勇.电针对大鼠局灶脑缺血再灌注后脑内血管生长因子和血管抑制因子表达的影响[J].中国针灸,2007,27(2):129.
[38]毛庆菊,陈邦国.电针对局灶性脑缺血再灌注大鼠大脑皮层微血管超微结构及血管内皮生长因子表达的影响[J].针刺研究,2012,37(6):476.
[39]张业贵,熊克仁.电针联合复方丹参片对慢性脑缺血大鼠海马CA1区脑源性神经营养因子和血管内皮生长因子表达的影响[J].中国中西医结合杂志,2012,32(5):646.
[40]谢宸宸,罗勇,高祥,等.电针对局灶脑缺血/再灌注模型大鼠缺血海马区血管再生的影响及其机制[J].中国实验动物学报,2014,22(4):41-46.
[2]苟芸,黄国伟,赵亚倩,等.同型半胱氨酸对大鼠局灶性脑缺血后血管再生的影响[J].天津医药,2016,44(1):5.
[3]郭建文,李俊雅,黄燕.调节“脑中血海”法联合骨髓间充质干细胞移植对大鼠缺血脑组织血管再生的影响[J].中西医结合学报,2009,7(8):763-768.
[4]惠娟,韩军良.脑缺血损伤后血管再生的研究进展[J].国际神经病学神经外科学杂志,2015,42(2):193.
[5]徐晓明,尤艳利,周爽.针刺促脑缺血后血管新生的研究进展[J].中华中医药学刊,2014,32(1):63.
[6]Trevor DC,Amanda RJ,Ethan CB,et al.Vascular endothelial growth factor:Therapeutic possibilities and challenges for the treatment of ischemia[J].Cytokine,2015,71(2):385-392.
[7]Ju R,Wen Y,Gou R,et al.The experimental therapy on brain ischemia by improvement of local angiogenesis with tissue engineering in themouse[J].Cell Transplant,2014,23(Sup-pl1):83-95.
[8]Zhu Y,Lee C,Shen F,et al.Angiopoietin-2 facilitates vascular endothelial growth factor-induced angiogenesis in the mature mouse brain[J].Stroke,2005,36(7):1533-1537.
[9]Murakami M,Nguyen LT,Zhuang ZW,et al.The FGF sys-tem has a key role in regulating vascular integrity[J].J Clin In-vest,2008,118(10):3355-3366.
[10]周盛年,姜维.浅谈缺血性卒中二级预防[J].中国现代神经疾病杂,2015,15(3):171-176.
[11]凌莉,张素平,吉章阁,等.外源性基质细胞衍生因子-1α对大鼠脑梗死后远隔部位细胞增殖和血管再生的影响[J].中国神经精神疾病杂志,2013,39(10):587-591.
[12]马甲,李连标,徐俊,等.血浆同型半胱氨酸与慢性脑缺血的相关性分析[J].现代实用医学,2016,28(4):453.
[13]苗江永,祝春华,王力娜,等.PI3-K/Akt通路在脑缺血治疗中的调控机制研究[J].脑与神经疾病杂志,2013,21(1):45.
[14]Zhang E,Feng X,Liu F,et al.Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein in-duced HIF-1alpha,VEGF,and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells[J].PLoS One,2014,9:e103440.
[15]Caron A,Richard D,Laplante M.The roles of m TOR complexes in lipid metabolism[J].Annu Rev Nutr,2015,35:321-348.
[16]Dodd KM,Yang J,Shen MH,et al.m TORC1 drives HIF-1alpha and VEGF-Asignalling via multiple mechanisms involving 4E-BP1,S6K1 and STAT3[J].Oncogene,2015,34:2239-2250.
[17]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].山东方大学学报(医学版),2015,53(4):32-35.
[18]Gherghe CM,Duan J,Gong J,et al.Wnt1 is a proangio-genic molecule,enhances human endothelial progenitorfunction,and increases blood flow boischemic limbs in aHGF-dependent manner[J].FASEB J,2011,25(6):1836-1843.
[19]薛金龙,石淑先,孙芳玲,等.Wnt信号通路及相关神经因子对神经再生的影响[J].中国比较医学杂志,2013,23(9):80-6.
[20]Xing XS,Liu F,He ZY.Akt regulatesβ-catenin in a rat model offocal cerebral ischemia-reperfusion injury[J].Molecul Med R eports,2015,11:3122-8.
[21]罗时鹏,余资江,肖朝伦,等.小鼠缺血/再灌注损伤后海马齿状回β-catenin、Cyclin D1的表达变化[J].黔南民族医专学报,2013,26(1):9-13,20.
[22]周强,李朝晖.Notch信号通路在脑缺血的研究进展[J].临床与病理杂志,2015,35(3):452.
[23]Hellstrom M,Phng LK,Hofmann JJ,et al.Dll4 signalling through Notch1regulates formation of tip cells during angiogenesis[J].Nature,2007,445(7129):776-780.
[24]Kwon SM,Eguchi M,Wada M,et al.Specii c Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization[J].Circulation,2008,118(2):157-165.
[25]王荣,李长生.VEGF-Notch/Delta级联信号通路对脑缺血后血管新生的影响[J].山西中医学院学报,2010,11(1):66.
[26]何正光,陈刚,祝慧凤,等.葛根素注射液对大鼠脑缺血/再灌注损伤的保护作用[J].中国药理学通报,2011,27(8):1182.
[27]谭灵莉,崔丹丹,祝慧凤,等.梓醇对脑缺血后神经血管单元构筑的影响[J].中国药理学通报,2014,30(1):47.
[28]曽联婷,史明,惠娟,等.人参皂甙Rd通过PI3K/AKT/mTOR/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.
[29]高海军,白焕焕,雷廷,等.川芎嗪在脑缺血再灌注损伤中的保护作用[J].中国老年学杂志,2015,35(17):5019-5022.
[30]谭辉,王键,尹婷婷,等.脑络欣通方对脑缺血大鼠血管再生及局部脑血流量的影响[J].中国实验方剂学杂志,2015,21(22):21.
[31]俞丽华,王键,陈业农,等.3种中药复方对脑缺血再灌注大鼠脑组织细胞间黏附分子-1和血管内皮生子因子表达的影响[J].中国老年学杂志,2014,34(6):1544.
[32]田兆华,刘柏炎.补阳还五汤对局灶性脑缺血大鼠血管新生的影响[J].中国动脉硬化杂志,2010,18(3):193.
[33]刘柏炎,蔡光先,刘维,等.补阳还五汤对大鼠局灶性脑缺血后血管内皮生长因子及其受体Flk1的影响[J].中草药,2007,38(3):394.
[34]曲铁兵,俞天虹,刘志婷,等.补阳还五汤及其拆方对大鼠脑缺血后神经发生的影响[J].中国中西医结合杂志,2014,34(3):342.
[35]高红莉,王德才,曲晓兰,等.黄芪丹参配伍对局灶性脑缺血再灌注大鼠脑组织VEGF和bFGFmRNA表达的影响[J].中药药理与临床,2013,29(5):95-98.
[36]韩永升,徐银,韩咏竹,等.电针对局灶性脑缺血再灌注大鼠神经血管单元的保护作用[J].针刺研究,2013,38(3):173.
[37]马璟曦,罗勇.电针对大鼠局灶脑缺血再灌注后脑内血管生长因子和血管抑制因子表达的影响[J].中国针灸,2007,27(2):129.
[38]毛庆菊,陈邦国.电针对局灶性脑缺血再灌注大鼠大脑皮层微血管超微结构及血管内皮生长因子表达的影响[J].针刺研究,2012,37(6):476.
[39]张业贵,熊克仁.电针联合复方丹参片对慢性脑缺血大鼠海马CA1区脑源性神经营养因子和血管内皮生长因子表达的影响[J].中国中西医结合杂志,2012,32(5):646.
[40]谢宸宸,罗勇,高祥,等.电针对局灶脑缺血/再灌注模型大鼠缺血海马区血管再生的影响及其机制[J].中国实验动物学报,2014,22(4):41-46.