中药生殖毒性体外实验研究进展
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摘要
生殖毒性作为中药学重要研究内容之一,是中药安全性研究的重要组成部分。目前对中药生殖毒性研究评价主要采用国内外新药临床前安全性评价指南所推荐的三阶段试验,然而存在费用高、实验周期长等缺点。欧洲替代方法研究中心(ECVAM)所推荐的胚胎干细胞试验、胚胎细胞微团培养试验及全胚胎培养试验等体外替代试验已应用于中药生殖、胚胎毒性的研究。该文就中药单体或复方生殖毒性体外试验评价的现状,对体外替代试验方法及其优缺点、必要性等进行了讨论。
The reproductive toxicity which is as one of the most important research in Chinese materia medica takes an important place in Chinese medicine pre-clinical safety evaluation. At present,the threephases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. However,there exists lots of questions such as high cost and long experimental period. Alternative methods of whole embryos culture and embryonic stem cell and embryonic cell micromass culture recommended by ECVAM have been used in reproductive and embryo toxicity evaluations of traditional Chinese medicine. This article reviewed research progresses on reproductive toxicity of traditional Chinese medicine by alternative methods in vitro and discussed their advantages,disadvantages and the necessity etc.
The reproductive toxicity which is as one of the most important research in Chinese materia medica takes an important place in Chinese medicine pre-clinical safety evaluation. At present,the threephases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. However,there exists lots of questions such as high cost and long experimental period. Alternative methods of whole embryos culture and embryonic stem cell and embryonic cell micromass culture recommended by ECVAM have been used in reproductive and embryo toxicity evaluations of traditional Chinese medicine. This article reviewed research progresses on reproductive toxicity of traditional Chinese medicine by alternative methods in vitro and discussed their advantages,disadvantages and the necessity etc.
引文
[1]赵奎君,梁丽娟.中药保胎药研究现状及安全性评价[J].药物流行病学杂志,2010,19(12):699-702.
[2]韩佳寅,梁爱华,易艳,等.中药生殖毒性研究思路与方法[J].药学学报,2014,49(11):1499-1503.
[3]Wu C Q.Overview of developmental and reproductive toxicity research in China:history,funding mechanisms,and frontiers of the research[J].Birth Def(Part B),2010,89(1):9-17.
[4]赵丽颖.中药生殖发育及胚胎毒性试验研究进展[J].时珍国医国药,2015,26(3):697-698.
[5]苗明三,王灿.中药对生殖系统毒性的研究分析[J].时珍国医国药,2008,19(2):284-285.
[6]邱丽,骆世存,李明先.常用保胎中药生殖毒性的研究概况[J].河北医学,2010,16(2):235-237.
[7]王雅楠,宋殿荣.胚胎毒性体外试验的研究进展[J].国际生殖健康,2010,29(4):277-280.
[8]周会芳,王丽,张艳军,等.胚胎干细胞的代谢组学方法在毒理学中的应用进展[J].中国药理学通报,2011,27(2):149-151.
[9]Genschow E,Spielmann H,Scholz G,et al.The ECVAM international validation Study on in vitro embryotoxicity tests:results of the definitive phase and evaluation of prediction models[J].Altern Lab Anim,2002,30(2):151-176.
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[11]Seiler A E,Spielmann H.The validated embryonic stem cell test to predict embryotoxicity in vitro[J].Nat Protoc,2011,6(7):961.
[12]徐珊,汪受传.“妊娠禁忌”中药的研究思路与方法[J].中医儿科杂志,2012,8(1):47-49.
[13]宋殿荣,王雅楠,张崴,等.小半夏加茯苓汤含药血清对小鼠胚胎干细胞体外增殖及分化的影响[J].天津中医药,2011,28(6):486-488.
[14]于洲,严卫星,张连峰,等.应用胚胎干细胞实验模型对人参皂苷Rb1、Rg1发育毒性的初步研究[J].毒理学杂志,2008,22(3):173-176.
[15]张崴,宋殿荣,王雅楠.基于胚胎干细胞实验模型评价黄芩苷的胚胎毒性[J].中国药理学与毒理学杂志,2012,26(6):864-868.
[16]Li L Y,Cao F F,Su Z J,et al.Assessment of the four Chinese herbal extracts using the embryonic stem cell test[J].Mol Med Rep,2015,12(2):2348-2354.
[17]Wang J,Masika J,Zhou J,et al.Traditional Chinese medicine baicalin suppress m ESCs proliferation through inhibition of mi R-294 expression[J].Cell Physiol Biochem,2015,35(5):1868-1876.
[18]Nieden N,Ruf L,Kempka G,et al.Molecular markers in embryonic stem cells[J].Toxicology in Vitro,2001,15(4/5):455-461.
[19]Flick B,Klug S.Whole embryo culture:an important tool in developmental toxicology today[J].Current Pharmaceutical Design,2006,12(12):1467-1488.
[20]柳鹏,许雅君,殷惠军,等.人参皂苷Rb1对小鼠胚胎发育毒性的体外实验研究[J].卫生研究,2005,34(2):175-177.
[21]韩佳寅,梁爱华,易艳,等.应用全胚胎培养方法研究野百合碱对小鼠胚胎发育的影响[J].中国中药杂志,2011,36(4):484-487.
[22]韩佳寅,梁爱华,易艳.倒千里光碱对小鼠体外培养胚胎的发育毒性研究[J].中国中药杂志,2011,36(14):1901-1904.
[23]韩佳寅,易艳,梁爱华,等.千里光对小鼠体外培养胚胎的胚胎毒性研究[J].药学学报,2014,49(9):1267-1272.
[24]肖凯,严光焰,王莉,等,应用大鼠体外胚胎培养模型研究生草乌对胚胎发育的影响[J].四川大学学报:医学版,2008,39(3):441-444.
[25]Liu P,Yin H J,Xu Y J,et al.Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro[J].Toxicol in Vitro,2006,20(2):234.
[26]刘星,李啸红,王燕,等.菟丝子含药血清对大鼠肢芽细胞、骨形成蛋白2及Ⅱ型胶原表达的影响[J].山东大学学报:医学版,2014,529(7):37-40.
[27]刘星,李啸红,袁新校,等.菟丝子含药血清对大鼠肢芽软骨发育的影响[J].中国优生与遗传杂志,2013,21(5):37-39.
[28]Genschow E,Scholz G,Brown N,et al.Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study[J].In Vitro Mol Toxicol,2000,13:51-56.
[29]黄晓敏,谈勇.中药对生殖机能影响的研究进展[J].江苏中医药,2006,27(3):63-65.
[30]林娜,胡建平.中药胚胎毒性的研究现状和展望[J].中国中药杂志,2005,30(17):1317-1320.
[2]韩佳寅,梁爱华,易艳,等.中药生殖毒性研究思路与方法[J].药学学报,2014,49(11):1499-1503.
[3]Wu C Q.Overview of developmental and reproductive toxicity research in China:history,funding mechanisms,and frontiers of the research[J].Birth Def(Part B),2010,89(1):9-17.
[4]赵丽颖.中药生殖发育及胚胎毒性试验研究进展[J].时珍国医国药,2015,26(3):697-698.
[5]苗明三,王灿.中药对生殖系统毒性的研究分析[J].时珍国医国药,2008,19(2):284-285.
[6]邱丽,骆世存,李明先.常用保胎中药生殖毒性的研究概况[J].河北医学,2010,16(2):235-237.
[7]王雅楠,宋殿荣.胚胎毒性体外试验的研究进展[J].国际生殖健康,2010,29(4):277-280.
[8]周会芳,王丽,张艳军,等.胚胎干细胞的代谢组学方法在毒理学中的应用进展[J].中国药理学通报,2011,27(2):149-151.
[9]Genschow E,Spielmann H,Scholz G,et al.The ECVAM international validation Study on in vitro embryotoxicity tests:results of the definitive phase and evaluation of prediction models[J].Altern Lab Anim,2002,30(2):151-176.
[10]韩佳寅,梁爱华.全胚胎培养技术及其应用研究进展[J].中国中药杂志,2010,35(5):549-553.
[11]Seiler A E,Spielmann H.The validated embryonic stem cell test to predict embryotoxicity in vitro[J].Nat Protoc,2011,6(7):961.
[12]徐珊,汪受传.“妊娠禁忌”中药的研究思路与方法[J].中医儿科杂志,2012,8(1):47-49.
[13]宋殿荣,王雅楠,张崴,等.小半夏加茯苓汤含药血清对小鼠胚胎干细胞体外增殖及分化的影响[J].天津中医药,2011,28(6):486-488.
[14]于洲,严卫星,张连峰,等.应用胚胎干细胞实验模型对人参皂苷Rb1、Rg1发育毒性的初步研究[J].毒理学杂志,2008,22(3):173-176.
[15]张崴,宋殿荣,王雅楠.基于胚胎干细胞实验模型评价黄芩苷的胚胎毒性[J].中国药理学与毒理学杂志,2012,26(6):864-868.
[16]Li L Y,Cao F F,Su Z J,et al.Assessment of the four Chinese herbal extracts using the embryonic stem cell test[J].Mol Med Rep,2015,12(2):2348-2354.
[17]Wang J,Masika J,Zhou J,et al.Traditional Chinese medicine baicalin suppress m ESCs proliferation through inhibition of mi R-294 expression[J].Cell Physiol Biochem,2015,35(5):1868-1876.
[18]Nieden N,Ruf L,Kempka G,et al.Molecular markers in embryonic stem cells[J].Toxicology in Vitro,2001,15(4/5):455-461.
[19]Flick B,Klug S.Whole embryo culture:an important tool in developmental toxicology today[J].Current Pharmaceutical Design,2006,12(12):1467-1488.
[20]柳鹏,许雅君,殷惠军,等.人参皂苷Rb1对小鼠胚胎发育毒性的体外实验研究[J].卫生研究,2005,34(2):175-177.
[21]韩佳寅,梁爱华,易艳,等.应用全胚胎培养方法研究野百合碱对小鼠胚胎发育的影响[J].中国中药杂志,2011,36(4):484-487.
[22]韩佳寅,梁爱华,易艳.倒千里光碱对小鼠体外培养胚胎的发育毒性研究[J].中国中药杂志,2011,36(14):1901-1904.
[23]韩佳寅,易艳,梁爱华,等.千里光对小鼠体外培养胚胎的胚胎毒性研究[J].药学学报,2014,49(9):1267-1272.
[24]肖凯,严光焰,王莉,等,应用大鼠体外胚胎培养模型研究生草乌对胚胎发育的影响[J].四川大学学报:医学版,2008,39(3):441-444.
[25]Liu P,Yin H J,Xu Y J,et al.Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro[J].Toxicol in Vitro,2006,20(2):234.
[26]刘星,李啸红,王燕,等.菟丝子含药血清对大鼠肢芽细胞、骨形成蛋白2及Ⅱ型胶原表达的影响[J].山东大学学报:医学版,2014,529(7):37-40.
[27]刘星,李啸红,袁新校,等.菟丝子含药血清对大鼠肢芽软骨发育的影响[J].中国优生与遗传杂志,2013,21(5):37-39.
[28]Genschow E,Scholz G,Brown N,et al.Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study[J].In Vitro Mol Toxicol,2000,13:51-56.
[29]黄晓敏,谈勇.中药对生殖机能影响的研究进展[J].江苏中医药,2006,27(3):63-65.
[30]林娜,胡建平.中药胚胎毒性的研究现状和展望[J].中国中药杂志,2005,30(17):1317-1320.