活络效灵丹及其主要活性成分防治脑缺血的研究
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摘要
活血化瘀是中医药防治脑缺血最常用方法,活络效灵丹是活血化瘀的代表方之一。本研究详细阐述了活络效灵丹整方的动物实验、主要成分的动物实验和整方的临床实验的主要实验结果,提出目前活络效灵丹及其主要活性成分研究中存在的主要问题是结论中的靶点尚未能证实。设想从预防给药、组分配比、精准靶向治疗等方面对该方展开进一步研究,为确实发现该方新靶点,为创制基于该方药效的现代创新药物提供新思路,为复方各组分协同作用奠定基础。
Promoting blood circulation therapy is the most common method for prevention and treatment of cerebral ischemia by TCM, Huoluo Xiaoling Pellets is one of the representative prescription of it. This paper elaborates on the animal experiments of the Huoluo Xiaoling Pellets, the animal experiments of the main active components, and the clinical experiment of the Huoluo Xiaoling Pellets. It is proposed that the main problem is the target in the conclusion cannot be confirmed.It is envisaged to conduct further research on this side from aspects such as preventive drug delivery, group distribution ratio, and precise targeted therapy. This is to discover a new target for this prescription, provide new ideas for the creation of modern innovative drugs based on the efficacy of the prescription, and lay the foundation for the synergistic effect of prescription components.
Promoting blood circulation therapy is the most common method for prevention and treatment of cerebral ischemia by TCM, Huoluo Xiaoling Pellets is one of the representative prescription of it. This paper elaborates on the animal experiments of the Huoluo Xiaoling Pellets, the animal experiments of the main active components, and the clinical experiment of the Huoluo Xiaoling Pellets. It is proposed that the main problem is the target in the conclusion cannot be confirmed.It is envisaged to conduct further research on this side from aspects such as preventive drug delivery, group distribution ratio, and precise targeted therapy. This is to discover a new target for this prescription, provide new ideas for the creation of modern innovative drugs based on the efficacy of the prescription, and lay the foundation for the synergistic effect of prescription components.
引文
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[2] Portegies ML,Bos MJ,Hofman A,et al. Role of prestroke vascular pathology in long-term prognosis after stroke:the rotterdam study[J]. Stroke,2016,47(18):80-87.
[3]谭凯文,陈薇.活血化瘀法治疗缺血性中风的拓展与探讨[J].中西医结合心脑血管病杂志,2015,13(9):1130-1131.
[4]王云凯,杨医亚,李斌之.医学衷中参西录(上册)[M].石家庄:河北科学技术出版社,1985:自序,例言,313-315,307-322.
[5]金竹青.活络效灵丹通过抑制脑组织炎症反应对缺血性脑损伤的保护作用[J].浙江中医药大学学报,2013,27(9):1099-1102,1107.
[6] Yu H,Lee DY,Nanjundaiah SM,et al. Microarray analysis reveals the molecular basis of antiarthritic activity of huo-luoxiao-ling dan[J]. Evid Based Complement Alternat Med,2013:524746.
[7]韩向东,赵妍,黄云枫,等.活络效灵丹拆方对乳鼠心肌细胞缺氧/复氧损伤的保护作用研究[J].上海中医药杂志,2012,58(3):65-68.
[8]邓茹月,房玉涛.活络效灵丹治疗心血管疾病的研究进展[J].贵阳中医学院学报,2014,36(3):142-144.
[9] Ren ZK,Zhang RP,Li YY,et al. Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo[J]. Int J Mol Med,2017,40(5):1444-1456.
[10] Cheng CY,Su SY,Tang NY,et al. Ferulic acid inhibits nitric oxide-induced apoptosis by enhancing GABA(B1)receptor expression in transient focal cerebral ischemia in rats[J]. Acta Pharmacol Sin,2010,31(8):889-899.
[11]韦玮,龚苏晓,张铁军,等.当归多糖类成分及其药理作用研究进展[J].药物评价研究,2009,32(2):130-134.
[12]林国芳.当归多糖对脑缺血再灌注损伤大鼠海马神经元的保护作用[J].中草药,2015,46(4):558-561.
[13]甘文忠,张盛.当归多糖对脑梗死模型大鼠血脑屏障通透性的影响[J].中医学报,2016,31(3):402-404.
[14]方针,廖维靖,雷涛,等.当归多糖与川芎嗪配伍对大鼠脑缺血再灌注后血管生成的影响[J].中国康复医学杂志,2014,29(11):1006-1009,1015.
[15] Zhan F,Lu Y,Wu X,et al. Ligustilide alleviates braindamage and improves cognitive function in rats of chroniccerebral hypoperfusion[J]. J Ethnopharmacology,2012,144(2):313-321.
[16]桑纳,王平汉,杜俊蓉.藁本内酯对小鼠海马区损伤的保护作用及其作用机制[J].华西药学杂志,2016,31(3):245-247.
[17] Lam BY,Lo AC,Sun X,et al. Neuroprotective effects of tanshinones on transient focal cerebral ischemia in mice[J].Phytomedicine,2003,132(10):286-291.
[18] Dong K,Xu W,Yang J,et al. Neuroprotective effects of TahshinoneⅡA on permanent focal cerebral ischemia in mice[J]. Phytother Res,2009,82(23):608-613.
[19]温蒲圆,杨凤真,王芳,等.丹参酮ⅡA对I/R大鼠脑组织GFAP、ATPase与PDI的调控研究[J].中药材,2012,35(10):1628-1632.
[20]蔡琳,易小波,袁利邦,等.丹参酮ⅡA通过NLRP3炎症体信号通路对小胶质细胞糖氧剥夺/再灌注损伤的保护作用[J].四川大学学报:医学版,2016,47(5):660-664.
[21]蔡青,黄淑芸,谭俊珍,等.丹参酮B钠盐对脑缺血再灌注损伤大鼠海马不同亚区NMDAR1蛋白表达的影响[J].中国中西医结合杂志,2012,32(8):1073-1076.
[22]陈广斌,陈华萍,吴铁,等.丹参素对新生大鼠缺氧缺血性脑损伤组织iNOS、NOS、NO的影响[J].中国医院药学杂志,2008,28(16):1329-1332.
[23]林少珠,陈广斌,吴铁,等.丹参素对新生大鼠缺氧缺血性脑损伤脑组织SOD、MDA的影响[J].中国实用医药,2012,7(24):12-14.
[24] Chao G,Ying Y,Jianlin D,et al. Neuroprotective effect and underlying mechanism of sodium danshensu[3-(3,4-dihydroxyphenyl)lactic acid from Radix and Rhizoma Salviae miltiorrhizae=Danshen] against cerebral ischemia and reperfusion injury in rats[J]. Phytomedicine,2015,22(2):283-289.
[25] Zhuang P,Wan Y,Geng S,et al. Salvianolic Acids for Injection(SAFI)suppresses inflammatory responses in activated microglia to attenuate brain damage in focal cerebral ischemia[J]. J Ethnopharmacol,2017,198(2):194-204.
[26]娄峥,周雅倩,徐献,等.丹参乙酸镁减轻脑缺血/再灌注诱导的神经细胞凋亡作用及机制[J].中南医学科学杂志,2017,45(5):465-470.
[27]蔡红蝶,宿树兰,周卫,等.乳香属药用植物中乳香酸类化学成分、生物活性及其作用机制研究进展[J].中草药,2016,47(12):2175-2181.
[28] Shen T,Li gH,Wang XN,et al. The genus Commiphora:Areview of its traditional uses,phytochemistry and pharma-cology[J]. J Ethnopharmacol,2012,142(2):319-330.
[29]顾平.丹参酮ⅡA磺酸钠注射液对老年缺血性脑卒中患者超敏C反应蛋白和白细胞介素-8水平的影响及疗效[J].中国老年学杂志,2012,32(8):1674-1675.
[30]李中方.复方丹参滴丸中西医结合治疗缺血性脑中风的疗效观察[J].山西中医,2017,33(10):37-38.
[31]王光浩,张敬芳,熊永梅.丹参与阿魏酸钠治疗急性脑梗死的临床疗效比较[J].微循环学杂志,2015,25(1):75-76.
[32]文贵斌.丹参多酚酸盐治疗对缺血性脑卒中患者外周血Bcl-2、BAX、Caspase-3分子表达的影响及其与神经功能的相关性[J].海南医学院学报,2017,23(9):1279-1282.
[33]徐英姿.当归注射液治疗急性缺血性脑卒中的疗效及对血液流变性影响分析[J].中国现代药物应用,2016,10(5):160-161.
[34]胡国恒,祝美珍.活血化瘀法防治脑缺血损伤的理论探讨[J].中华中医药杂志,2008,23(6):513-515.
[35]周琴,廖维靖,杨万同.当归与阿魏酸钠对促进局灶性脑缺血再灌注后神经功能恢复作用的比较[J].武汉大学学报:医学版,2007,50(3):332-335,340.
[2] Portegies ML,Bos MJ,Hofman A,et al. Role of prestroke vascular pathology in long-term prognosis after stroke:the rotterdam study[J]. Stroke,2016,47(18):80-87.
[3]谭凯文,陈薇.活血化瘀法治疗缺血性中风的拓展与探讨[J].中西医结合心脑血管病杂志,2015,13(9):1130-1131.
[4]王云凯,杨医亚,李斌之.医学衷中参西录(上册)[M].石家庄:河北科学技术出版社,1985:自序,例言,313-315,307-322.
[5]金竹青.活络效灵丹通过抑制脑组织炎症反应对缺血性脑损伤的保护作用[J].浙江中医药大学学报,2013,27(9):1099-1102,1107.
[6] Yu H,Lee DY,Nanjundaiah SM,et al. Microarray analysis reveals the molecular basis of antiarthritic activity of huo-luoxiao-ling dan[J]. Evid Based Complement Alternat Med,2013:524746.
[7]韩向东,赵妍,黄云枫,等.活络效灵丹拆方对乳鼠心肌细胞缺氧/复氧损伤的保护作用研究[J].上海中医药杂志,2012,58(3):65-68.
[8]邓茹月,房玉涛.活络效灵丹治疗心血管疾病的研究进展[J].贵阳中医学院学报,2014,36(3):142-144.
[9] Ren ZK,Zhang RP,Li YY,et al. Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo[J]. Int J Mol Med,2017,40(5):1444-1456.
[10] Cheng CY,Su SY,Tang NY,et al. Ferulic acid inhibits nitric oxide-induced apoptosis by enhancing GABA(B1)receptor expression in transient focal cerebral ischemia in rats[J]. Acta Pharmacol Sin,2010,31(8):889-899.
[11]韦玮,龚苏晓,张铁军,等.当归多糖类成分及其药理作用研究进展[J].药物评价研究,2009,32(2):130-134.
[12]林国芳.当归多糖对脑缺血再灌注损伤大鼠海马神经元的保护作用[J].中草药,2015,46(4):558-561.
[13]甘文忠,张盛.当归多糖对脑梗死模型大鼠血脑屏障通透性的影响[J].中医学报,2016,31(3):402-404.
[14]方针,廖维靖,雷涛,等.当归多糖与川芎嗪配伍对大鼠脑缺血再灌注后血管生成的影响[J].中国康复医学杂志,2014,29(11):1006-1009,1015.
[15] Zhan F,Lu Y,Wu X,et al. Ligustilide alleviates braindamage and improves cognitive function in rats of chroniccerebral hypoperfusion[J]. J Ethnopharmacology,2012,144(2):313-321.
[16]桑纳,王平汉,杜俊蓉.藁本内酯对小鼠海马区损伤的保护作用及其作用机制[J].华西药学杂志,2016,31(3):245-247.
[17] Lam BY,Lo AC,Sun X,et al. Neuroprotective effects of tanshinones on transient focal cerebral ischemia in mice[J].Phytomedicine,2003,132(10):286-291.
[18] Dong K,Xu W,Yang J,et al. Neuroprotective effects of TahshinoneⅡA on permanent focal cerebral ischemia in mice[J]. Phytother Res,2009,82(23):608-613.
[19]温蒲圆,杨凤真,王芳,等.丹参酮ⅡA对I/R大鼠脑组织GFAP、ATPase与PDI的调控研究[J].中药材,2012,35(10):1628-1632.
[20]蔡琳,易小波,袁利邦,等.丹参酮ⅡA通过NLRP3炎症体信号通路对小胶质细胞糖氧剥夺/再灌注损伤的保护作用[J].四川大学学报:医学版,2016,47(5):660-664.
[21]蔡青,黄淑芸,谭俊珍,等.丹参酮B钠盐对脑缺血再灌注损伤大鼠海马不同亚区NMDAR1蛋白表达的影响[J].中国中西医结合杂志,2012,32(8):1073-1076.
[22]陈广斌,陈华萍,吴铁,等.丹参素对新生大鼠缺氧缺血性脑损伤组织iNOS、NOS、NO的影响[J].中国医院药学杂志,2008,28(16):1329-1332.
[23]林少珠,陈广斌,吴铁,等.丹参素对新生大鼠缺氧缺血性脑损伤脑组织SOD、MDA的影响[J].中国实用医药,2012,7(24):12-14.
[24] Chao G,Ying Y,Jianlin D,et al. Neuroprotective effect and underlying mechanism of sodium danshensu[3-(3,4-dihydroxyphenyl)lactic acid from Radix and Rhizoma Salviae miltiorrhizae=Danshen] against cerebral ischemia and reperfusion injury in rats[J]. Phytomedicine,2015,22(2):283-289.
[25] Zhuang P,Wan Y,Geng S,et al. Salvianolic Acids for Injection(SAFI)suppresses inflammatory responses in activated microglia to attenuate brain damage in focal cerebral ischemia[J]. J Ethnopharmacol,2017,198(2):194-204.
[26]娄峥,周雅倩,徐献,等.丹参乙酸镁减轻脑缺血/再灌注诱导的神经细胞凋亡作用及机制[J].中南医学科学杂志,2017,45(5):465-470.
[27]蔡红蝶,宿树兰,周卫,等.乳香属药用植物中乳香酸类化学成分、生物活性及其作用机制研究进展[J].中草药,2016,47(12):2175-2181.
[28] Shen T,Li gH,Wang XN,et al. The genus Commiphora:Areview of its traditional uses,phytochemistry and pharma-cology[J]. J Ethnopharmacol,2012,142(2):319-330.
[29]顾平.丹参酮ⅡA磺酸钠注射液对老年缺血性脑卒中患者超敏C反应蛋白和白细胞介素-8水平的影响及疗效[J].中国老年学杂志,2012,32(8):1674-1675.
[30]李中方.复方丹参滴丸中西医结合治疗缺血性脑中风的疗效观察[J].山西中医,2017,33(10):37-38.
[31]王光浩,张敬芳,熊永梅.丹参与阿魏酸钠治疗急性脑梗死的临床疗效比较[J].微循环学杂志,2015,25(1):75-76.
[32]文贵斌.丹参多酚酸盐治疗对缺血性脑卒中患者外周血Bcl-2、BAX、Caspase-3分子表达的影响及其与神经功能的相关性[J].海南医学院学报,2017,23(9):1279-1282.
[33]徐英姿.当归注射液治疗急性缺血性脑卒中的疗效及对血液流变性影响分析[J].中国现代药物应用,2016,10(5):160-161.
[34]胡国恒,祝美珍.活血化瘀法防治脑缺血损伤的理论探讨[J].中华中医药杂志,2008,23(6):513-515.
[35]周琴,廖维靖,杨万同.当归与阿魏酸钠对促进局灶性脑缺血再灌注后神经功能恢复作用的比较[J].武汉大学学报:医学版,2007,50(3):332-335,340.
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