中药胚胎毒性在体外实验中的研究进展
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摘要
中药在妊娠期运用广泛,但中药的妊娠毒性和胚胎毒性历来争议较大,体外替代实验是近年来逐渐发展和建立起来的研究药物胚胎和发育毒性的新方法,该文分别从胚胎干细胞实验(EST)、动物胚胎肢芽体外培养、全胚胎培养(WEC)技术在中药胚胎毒性研究中的应用进行综述。
Traditional Chinese medicine( TCM) is widely used during pregnancy,but its embryotoxicity and toxicity of pregnancy has always been controversial. Experiment study in vitro,a new method,is established and developed gradually in recent years for research on embryotoxicity and developmental toxicity. This paper summarizes embryonic stem cells( EST),animal embryo limb buds outside culture and the whole embryo culture( WEC) technology respectively in the application of traditional Chinese medicine( TCM) embryotoxicity research.
Traditional Chinese medicine( TCM) is widely used during pregnancy,but its embryotoxicity and toxicity of pregnancy has always been controversial. Experiment study in vitro,a new method,is established and developed gradually in recent years for research on embryotoxicity and developmental toxicity. This paper summarizes embryonic stem cells( EST),animal embryo limb buds outside culture and the whole embryo culture( WEC) technology respectively in the application of traditional Chinese medicine( TCM) embryotoxicity research.
引文
[1]Xiaoming Zhu,Xiuyu Qi,Jiahu Hao,et al.Pattern of drug use during the first trimester among Chinese women:Data from a populationbased cohort study[J].Eur J Clin Pharmacol,2010,66(5):511-518.
[2]张川,张伶俐,陈力,等.妊娠期用药调查研究的系统评价[J].中国药学杂志,2012,47(11):858-862.
[3]Chuang CH,Chang PJ,Hsieh WS,et al.Chinese herbal medicine use in Taiwan during pregnancy and the postpartum period:a populationbased cohort study[J].Int J Nurs Stud,2009,46(6):787-795.
[4]Evans MJ,Kaufman MH.Establishment in culture of pluripotential cells from mouse embryos[J].Nature,1981,292:154-156.
[5]Brown S,Teo A,Pauklin S,et al.Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors[J].Stem Cells,2011,29(8):1176-1185.
[6]Sokol SY.Maintaining embryonic stem cell pluripotency with Wilt signaling[J].Development,2011,138(20):4341-4350.
[7]M Esmaeili,K Ghaedi,A shoaraye Nejati,et al.Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11βknock-down[J].Neuroscience,2015,312:35-47.
[8]Xiugong Gao,Robert L,Sprando,et al.Transcriptomic changes in mouse embryonic stem cells exposed to thalidomide during spontaneous differentiation[J].Data in Brief,2015,4:199-202.
[9]Scholz G,Genschow E,Pohl I,et al.Prevalidation of the Embryonic Stem Cell Test(EST)-A New In Vitro Embryotoxicity Test[J].Toxicology in Vitro,1999,13:675-681.
[10]Spielmann H,Seiler A,Bremer S,et al.The practical application of three validated in vitro embryotoxicity tests.The report and recommendations of an ECVAM/ZEBET workshop(ECVAM workshop 57)[J].ATLA,2006,34(5):527-538.
[11]安红梅,胡兵,史云峰,等.补肾阳中药对小鼠胚胎干细胞活动及相关基因表达的影响[J].中华中医药杂志,2008,23(9):774-775.
[12]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.
[13]张崴,宋殿荣,王雅楠,等.基于妊娠期应用中药安全性评价体系探讨黄芩的胚胎毒性[J].天津中医药,2013,30(7):431-435.
[14]耿传营,徐波,李红艳,等.3种中药单体对卵巢癌端粒酶活性于放射敏感性的影响[J].中华中医药杂志,2009,24(10):1372-1375.
[15]王炜,黄赞松,黄衍强,等.中药单体逆转肿瘤多药耐药的研究进展[J].世界华人消化杂志,2013,21(17):1623-1629.
[16]Zhang Li-na,Wang Yuan-yuan,Huang Ying-juan,et al.Neuroprotective effect of Chinese herbal monomers and extracts via activation of Nrf2 signal pathway[J].中国组织工程研究,2015,19(11):1774-1781.
[17]李君丽,孙蕾,席忠新,等.中药单体成分治疗类风湿关节炎研究进展[J].中药材,2012,35(8):1355-1360.
[18]方海琴,于洲,杨嵘,等.胚胎干细胞试验模型用于白藜芦醇胚胎发育毒性的评价[J].毒理学杂志,2013,27(2):89.
[19]丁玲.淫羊藿苷促小鼠胚胎干细胞体外分化为心肌细胞的相关机制研究[D].杭州:浙江大学,2007.
[20]Ding L,Liang XG,Zhu DY,et al.Icariin promotes expression of PGC-1alpha,PPARalpha,and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro[J].Acta Pharmacol Sin,2007,28(10):1541-1549.
[21]Flint OP,Orton TC.An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells[J].Toxicol Appl Pharmacol,1984,76(2):383-395.
[22]邹聪聪,李啸红.动物胚胎肢芽培养技术在发育毒性研究中的应用[J].中国优生与遗传杂志,2015,23(5):130.
[23]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.
[24]Tahereh TAL,AEI-KHOZANI,Zahra VOJDANI,et al.Toxic Effects of Elaeagnus angustifolia Fruit Extract on Chondrogenesis and Osteogenesis in Mouse Limb Buds[J].Tokai J Exp Clin Med,2011,36(3):63-70.
[25]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.
[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,2014,52(7):37.
[27]Brown NA,Fabro S.Quantitation of rat embryonic development in vitro:A morphological scoring system[J].Teratology,1981,24(1):65-78.
[28]Flick B,Klug S.Whole embryo culture:An important tool in developmental toxicology today[J].Curr Pharm Desi,2006,12:1467.
[29]赵树芬,保毓书,张兰芬,等.应用啮齿类动物全胚胎培养方法筛查致畸原的研究[J].卫生毒理学杂志,1993,1:1.
[30]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,2008,39(3):441.
[31]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.
[32]Liu P,Yin HJ,Xu YJ,et al.Effects of ginsenoside Rg1 on postimplantation ratand mouse embryos cultured in vitro[J].Toxicol In Vitro,2006,20:234.
[2]张川,张伶俐,陈力,等.妊娠期用药调查研究的系统评价[J].中国药学杂志,2012,47(11):858-862.
[3]Chuang CH,Chang PJ,Hsieh WS,et al.Chinese herbal medicine use in Taiwan during pregnancy and the postpartum period:a populationbased cohort study[J].Int J Nurs Stud,2009,46(6):787-795.
[4]Evans MJ,Kaufman MH.Establishment in culture of pluripotential cells from mouse embryos[J].Nature,1981,292:154-156.
[5]Brown S,Teo A,Pauklin S,et al.Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors[J].Stem Cells,2011,29(8):1176-1185.
[6]Sokol SY.Maintaining embryonic stem cell pluripotency with Wilt signaling[J].Development,2011,138(20):4341-4350.
[7]M Esmaeili,K Ghaedi,A shoaraye Nejati,et al.Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11βknock-down[J].Neuroscience,2015,312:35-47.
[8]Xiugong Gao,Robert L,Sprando,et al.Transcriptomic changes in mouse embryonic stem cells exposed to thalidomide during spontaneous differentiation[J].Data in Brief,2015,4:199-202.
[9]Scholz G,Genschow E,Pohl I,et al.Prevalidation of the Embryonic Stem Cell Test(EST)-A New In Vitro Embryotoxicity Test[J].Toxicology in Vitro,1999,13:675-681.
[10]Spielmann H,Seiler A,Bremer S,et al.The practical application of three validated in vitro embryotoxicity tests.The report and recommendations of an ECVAM/ZEBET workshop(ECVAM workshop 57)[J].ATLA,2006,34(5):527-538.
[11]安红梅,胡兵,史云峰,等.补肾阳中药对小鼠胚胎干细胞活动及相关基因表达的影响[J].中华中医药杂志,2008,23(9):774-775.
[12]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.
[13]张崴,宋殿荣,王雅楠,等.基于妊娠期应用中药安全性评价体系探讨黄芩的胚胎毒性[J].天津中医药,2013,30(7):431-435.
[14]耿传营,徐波,李红艳,等.3种中药单体对卵巢癌端粒酶活性于放射敏感性的影响[J].中华中医药杂志,2009,24(10):1372-1375.
[15]王炜,黄赞松,黄衍强,等.中药单体逆转肿瘤多药耐药的研究进展[J].世界华人消化杂志,2013,21(17):1623-1629.
[16]Zhang Li-na,Wang Yuan-yuan,Huang Ying-juan,et al.Neuroprotective effect of Chinese herbal monomers and extracts via activation of Nrf2 signal pathway[J].中国组织工程研究,2015,19(11):1774-1781.
[17]李君丽,孙蕾,席忠新,等.中药单体成分治疗类风湿关节炎研究进展[J].中药材,2012,35(8):1355-1360.
[18]方海琴,于洲,杨嵘,等.胚胎干细胞试验模型用于白藜芦醇胚胎发育毒性的评价[J].毒理学杂志,2013,27(2):89.
[19]丁玲.淫羊藿苷促小鼠胚胎干细胞体外分化为心肌细胞的相关机制研究[D].杭州:浙江大学,2007.
[20]Ding L,Liang XG,Zhu DY,et al.Icariin promotes expression of PGC-1alpha,PPARalpha,and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro[J].Acta Pharmacol Sin,2007,28(10):1541-1549.
[21]Flint OP,Orton TC.An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells[J].Toxicol Appl Pharmacol,1984,76(2):383-395.
[22]邹聪聪,李啸红.动物胚胎肢芽培养技术在发育毒性研究中的应用[J].中国优生与遗传杂志,2015,23(5):130.
[23]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.
[24]Tahereh TAL,AEI-KHOZANI,Zahra VOJDANI,et al.Toxic Effects of Elaeagnus angustifolia Fruit Extract on Chondrogenesis and Osteogenesis in Mouse Limb Buds[J].Tokai J Exp Clin Med,2011,36(3):63-70.
[25]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.
[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,2014,52(7):37.
[27]Brown NA,Fabro S.Quantitation of rat embryonic development in vitro:A morphological scoring system[J].Teratology,1981,24(1):65-78.
[28]Flick B,Klug S.Whole embryo culture:An important tool in developmental toxicology today[J].Curr Pharm Desi,2006,12:1467.
[29]赵树芬,保毓书,张兰芬,等.应用啮齿类动物全胚胎培养方法筛查致畸原的研究[J].卫生毒理学杂志,1993,1:1.
[30]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,2008,39(3):441.
[31]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.
[32]Liu P,Yin HJ,Xu YJ,et al.Effects of ginsenoside Rg1 on postimplantation ratand mouse embryos cultured in vitro[J].Toxicol In Vitro,2006,20:234.