铀的生殖毒性效应及作用机制研究进展
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摘要
目的铀作为一种重金属材料,虽然在民事和军事活动中得到应用,但同时也造成了环境污染和人员伤害。为了解以及减轻这种伤害,学者们通过构建动物模型,对其损伤效应进行了研究,发现铀进入动物体内后,会在体内蓄积,进而对机体产生损伤,其中主要的蓄积器官是肾、骨骼和生殖器官等。生殖器官作为铀作用的敏感器官,引起了专家们的注意,并对铀暴露的生殖毒性展开了研究,发现铀毒性作用的程度与铀暴露时间、剂量和方式有关,在一定暴露条件下,可通过改变体内性激素水平、紊乱生殖有关的基因或蛋白表达和过度产生氧化应激等机制,对机体产生毒性效应,使亲代的怀孕分娩率下降、相关生殖细胞发生病理组织学改变和对子代产生遗传生殖毒性等,进而影响其生殖系统功能,损害机体的健康。
Objective Uranium,as a heavy metal material,has been used in civil and military activities in China,but it has also caused environmental pollution and human injury.In order to understand and mitigate this injury,scholars studied the damage effect of uranium through building animal models,and found that when uranium enters the animal body,it will accumulate in the body and cause damage to the body,among which the main accumulation organs are kidneys,bones,reproductive organs and so on.Sensitive organs of the role of reproductive organs is uranium,which attracted the attention of the experts,and expand the uranium exposed reproductive toxicity research.They found that the degree of toxicity of uranium is related to the time,dose and mode of uranium exposure,under certain exposure conditions,by changing the sex hormone levels in vivo,the expression of genes or proteins related to the reproductive disorders and excessive produce the mechanism,such as oxidative stress on the toxicity effect,decrease of childbirth pregnant,related to germ cell pathological histology change,and produce genetic reproductive toxicity to the offspring etc.,which affect the reproductive system function,damage the health of the body.
Objective Uranium,as a heavy metal material,has been used in civil and military activities in China,but it has also caused environmental pollution and human injury.In order to understand and mitigate this injury,scholars studied the damage effect of uranium through building animal models,and found that when uranium enters the animal body,it will accumulate in the body and cause damage to the body,among which the main accumulation organs are kidneys,bones,reproductive organs and so on.Sensitive organs of the role of reproductive organs is uranium,which attracted the attention of the experts,and expand the uranium exposed reproductive toxicity research.They found that the degree of toxicity of uranium is related to the time,dose and mode of uranium exposure,under certain exposure conditions,by changing the sex hormone levels in vivo,the expression of genes or proteins related to the reproductive disorders and excessive produce the mechanism,such as oxidative stress on the toxicity effect,decrease of childbirth pregnant,related to germ cell pathological histology change,and produce genetic reproductive toxicity to the offspring etc.,which affect the reproductive system function,damage the health of the body.
引文
[1]郝玉徽,刘聪,粟永萍,等.铀的急性肾毒性及其救治方法研究进展[J].中华放射医学与防护杂志,2013,33(2):207-211.doi:10.3760/cma.j.issn.0254-5098.2013.02.026.
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[3]Hindi R,Brugge D,Panikkar B.Teratogenicity of depleted uranium aerosols:a review from an epidemiological perspective[J].Environ Health,2005,4:17.doi:10.1186/1476-069X-4-17.
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[5]李蓉,粟永萍,徐辉,等.大鼠长期摄入贫铀污染食物后的生殖遗传毒性、靶器官损伤研究[J].生物物理学报,2009,25(S1):462.
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[7]白杨,刘晋祎,曹佳,等.贫铀对小鼠睾丸生精细胞和精子遗传损伤的初步研究[J].第三军医大学学报,2003,25(19):1722-1724.doi:10.3321/j.issn:1000-5404.2003.19.011.
[8]陈如松,国爱英,赵永昌,等.慢性铀中毒对小鼠生殖力及生精细胞染色体畸变的影响[J].核防护,1976(3):91-98.
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[11]Arfsten DP,Still KR,Wilfong ER,et al.Two-generation reproductive toxicity study of implanted depleted uranium(DU)in CD rats[J].JToxicol Environ Health Part A,2009,72(6):410-427.doi:10.1080/15287390802647344.
[12]Squibb KS,Mc Diarmid MA.Depleted uranium exposure and health effects in Gulf War veterans[J].Philos Trans R Soc Lond B Biol Sci,2006,361(1468):639-648.doi:10.1098/rstb.2006.1823.
[13]Mitchell SE,Caldwell CA,Gonzales G,et al.Effects of depleted uranium on survival,growth,and metamorphosis in the African clawed frog(Xenopus laevis)[J].J Toxicol Environ Health Part A,2005,68(11-12):951-965.doi:10.1080/15287390590912595.
[14]Domingo JL.Reproductive and developmental toxicity of natural and depleted uranium:a review[J].Reprod Toxicol,2001,15(6):603-609.doi:10.1016/s0890-6238(01)00181-2.
[15]Arfsten DP,Still KR,Ritchie GD.A review of the effects of uranium and depleted uranium exposure on reproduction and fetal development[J].Toxicol Ind Health,2001,17(5-10):180-191.doi:10.1191/0748233701th111oa.
[16]Linares V,Albina ML,Bellés M,et al.Combined action of uranium and stress in the rat.II.Effects on male reproduction[J].Toxicol Lett,2005,158(3):186-195.doi:10.1016/j.toxlet.2005.03.015.
[17]Angenard G,Muczynski V,Coffigny H,et al.In vitro effects of Uranium on human fetal germ cells[J].Reprod Toxicol,2011,31(4):470-476.doi:10.1016/j.reprotox.2010.12.058.
[18]朱寿彭,胡启跃,伦明跃.浓缩铀诱发生殖毒性研究[J].中华预防医学杂志,1994,28(4):219-222.doi:10.3760/j:issn:0253-9624.1994.04.020.
[19]Grignard E,Gueguen Y,Grison S,et al.Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism in rat[J].Int J Toxicol,2008,27(4):323-328.doi:10.1080/10915810802367057.
[20]Carreau S,de Vienne C,Galeraud-Denis I.Aromatase and estrogens in man reproduction:a review and latest advances[J].Adv Med Sci,2008,53(2):139-144.doi:10.2478/v10039-008-0022-z.
[21]Chandra J,Samali A,Orrenius S.Triggering and modulation of apoptosis by oxidative stress[J].Free Radic Biol Med,2000,29(3-4):323-333.doi:10.1016/s0891-5849(00)00302-6.
[22]张慧锋.细胞色素P450的研究进展[J].吉林医药学院学报,2005,6(3):174-177.doi:10.3969/j.issn.1673-2995.2005.03.024.
[23]程天民,粟永萍,徐辉,等.大鼠长期摄入贫铀对睾酮合成及St AR、P450scc基因表达的影响[J].中华放射医学与防护杂志,2009,29(1):13-16.doi:10.3760/cma.j.issn.0254-5098.2009.01.004.
[24]李积胜,张珩,王华仁.贫铀对大鼠睾丸诱导型一氧化氮合酶基因表达的影响[J].中华男科学杂志,2005,11(9):655-657.doi:10.3969/j.issn.1009-3591.2005.09.004.
[25]Mc Diarmid MA,Engelhardt S,Oliver M,et al.Health effects of depleted uranium on exposed Gulf War veterans:a 10-year follow-up[J].JToxicol Environ Health Part A,2004,67(4):277-296.doi:10.1080/15287390490273541.
[26]Poisson C,Stefani J,Manens L,et al.Chronic uranium exposure dosedependently induces glutathione in rats without any nephrotoxicity[J].Free Radic Res,2014,48(10):1218-1231.doi:10.3109/10715762.2014.945441.
[27]Wade-Gueye NM,Delissen O,Gourmelon P,et al.Chronic exposure to natural uranium via drinking water affects bone in growing rats[J].Biochim Biophys Acta,2012,1820(7):1121-1127.doi:10.1016/j.bbagen.2012.04.019.
[28]Dinocourt C,Legrand M,Dublineau I,et al.The neurotoxicology of uranium[J].Toxicology,2015,337:58-71.doi:10.1016/j.tox.2015.08.004.
[29]Sztajnkrycer MD,Otten EJ.Chemical and radiological toxicity of depleted uranium[J].Mil Med,2004,169(3):212-216.doi:10.7205/milmed.169.3.212.
[30]张晓菲,赵长琦,刘丽宏.贫铀的危害及铀促排剂的研究进展[J].北京师范大学学报,2010,46(4):517-521.
[31]Mc Diarmid MA,Engelhardt SM,Dorsey CD,et al.Longitudinal health surveillance in a cohort of Gulf War veterans 18 years after first exposure to depleted uranium[J].J Toxicol Environ Health Part A,2011,74(10):678-691.doi:10.1080/15287394.2011.539138.
[32]Mc Diarmid MA,Engelhardt SM,Dorsey CD,et al.Surveillance results of depleted uranium-exposed Gulf War I veterans:sixteen years of follow-up[J].J Toxicol Environ Health Part A,2009,72(1):14-29.doi:10.1080/15287390802445400.
[2]Priest ND.Toxicity of depleted uranium[J].Lancet,2001,357(9252):244-246.doi:10.1016/s0140-6736(00)03605-9.
[3]Hindi R,Brugge D,Panikkar B.Teratogenicity of depleted uranium aerosols:a review from an epidemiological perspective[J].Environ Health,2005,4:17.doi:10.1186/1476-069X-4-17.
[4]艾国平,李蓉,肖桃元,等.大鼠长期摄入贫铀后的病理形态学特点观察[J].解放军医学杂志,2007,32(10):1036-1039.doi:10.3321/j.issn:0577-7402.2007.10.011.
[5]李蓉,粟永萍,徐辉,等.大鼠长期摄入贫铀污染食物后的生殖遗传毒性、靶器官损伤研究[J].生物物理学报,2009,25(S1):462.
[6]Legendre A,Elie C,Ramambason C,et al.Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat[J].Toxicology,2016,368-369:58-68.doi:10.1016/j.tox.2016.08.014.
[7]白杨,刘晋祎,曹佳,等.贫铀对小鼠睾丸生精细胞和精子遗传损伤的初步研究[J].第三军医大学学报,2003,25(19):1722-1724.doi:10.3321/j.issn:1000-5404.2003.19.011.
[8]陈如松,国爱英,赵永昌,等.慢性铀中毒对小鼠生殖力及生精细胞染色体畸变的影响[J].核防护,1976(3):91-98.
[9]冷言冰.贫铀长期植入对大鼠生殖系统损伤效应的研究[J].现代预防医学,2008,35(9):1618-1620.doi:10.3969/j.issn.1003-8507.2008.09.007.
[10]Mc Clain DE,Benson KA,Dalton TK,et al.Health effects of embedded depleted uranium[J].Military Medicine,2002,167(Suppl 1):117-119.
[11]Arfsten DP,Still KR,Wilfong ER,et al.Two-generation reproductive toxicity study of implanted depleted uranium(DU)in CD rats[J].JToxicol Environ Health Part A,2009,72(6):410-427.doi:10.1080/15287390802647344.
[12]Squibb KS,Mc Diarmid MA.Depleted uranium exposure and health effects in Gulf War veterans[J].Philos Trans R Soc Lond B Biol Sci,2006,361(1468):639-648.doi:10.1098/rstb.2006.1823.
[13]Mitchell SE,Caldwell CA,Gonzales G,et al.Effects of depleted uranium on survival,growth,and metamorphosis in the African clawed frog(Xenopus laevis)[J].J Toxicol Environ Health Part A,2005,68(11-12):951-965.doi:10.1080/15287390590912595.
[14]Domingo JL.Reproductive and developmental toxicity of natural and depleted uranium:a review[J].Reprod Toxicol,2001,15(6):603-609.doi:10.1016/s0890-6238(01)00181-2.
[15]Arfsten DP,Still KR,Ritchie GD.A review of the effects of uranium and depleted uranium exposure on reproduction and fetal development[J].Toxicol Ind Health,2001,17(5-10):180-191.doi:10.1191/0748233701th111oa.
[16]Linares V,Albina ML,Bellés M,et al.Combined action of uranium and stress in the rat.II.Effects on male reproduction[J].Toxicol Lett,2005,158(3):186-195.doi:10.1016/j.toxlet.2005.03.015.
[17]Angenard G,Muczynski V,Coffigny H,et al.In vitro effects of Uranium on human fetal germ cells[J].Reprod Toxicol,2011,31(4):470-476.doi:10.1016/j.reprotox.2010.12.058.
[18]朱寿彭,胡启跃,伦明跃.浓缩铀诱发生殖毒性研究[J].中华预防医学杂志,1994,28(4):219-222.doi:10.3760/j:issn:0253-9624.1994.04.020.
[19]Grignard E,Gueguen Y,Grison S,et al.Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism in rat[J].Int J Toxicol,2008,27(4):323-328.doi:10.1080/10915810802367057.
[20]Carreau S,de Vienne C,Galeraud-Denis I.Aromatase and estrogens in man reproduction:a review and latest advances[J].Adv Med Sci,2008,53(2):139-144.doi:10.2478/v10039-008-0022-z.
[21]Chandra J,Samali A,Orrenius S.Triggering and modulation of apoptosis by oxidative stress[J].Free Radic Biol Med,2000,29(3-4):323-333.doi:10.1016/s0891-5849(00)00302-6.
[22]张慧锋.细胞色素P450的研究进展[J].吉林医药学院学报,2005,6(3):174-177.doi:10.3969/j.issn.1673-2995.2005.03.024.
[23]程天民,粟永萍,徐辉,等.大鼠长期摄入贫铀对睾酮合成及St AR、P450scc基因表达的影响[J].中华放射医学与防护杂志,2009,29(1):13-16.doi:10.3760/cma.j.issn.0254-5098.2009.01.004.
[24]李积胜,张珩,王华仁.贫铀对大鼠睾丸诱导型一氧化氮合酶基因表达的影响[J].中华男科学杂志,2005,11(9):655-657.doi:10.3969/j.issn.1009-3591.2005.09.004.
[25]Mc Diarmid MA,Engelhardt S,Oliver M,et al.Health effects of depleted uranium on exposed Gulf War veterans:a 10-year follow-up[J].JToxicol Environ Health Part A,2004,67(4):277-296.doi:10.1080/15287390490273541.
[26]Poisson C,Stefani J,Manens L,et al.Chronic uranium exposure dosedependently induces glutathione in rats without any nephrotoxicity[J].Free Radic Res,2014,48(10):1218-1231.doi:10.3109/10715762.2014.945441.
[27]Wade-Gueye NM,Delissen O,Gourmelon P,et al.Chronic exposure to natural uranium via drinking water affects bone in growing rats[J].Biochim Biophys Acta,2012,1820(7):1121-1127.doi:10.1016/j.bbagen.2012.04.019.
[28]Dinocourt C,Legrand M,Dublineau I,et al.The neurotoxicology of uranium[J].Toxicology,2015,337:58-71.doi:10.1016/j.tox.2015.08.004.
[29]Sztajnkrycer MD,Otten EJ.Chemical and radiological toxicity of depleted uranium[J].Mil Med,2004,169(3):212-216.doi:10.7205/milmed.169.3.212.
[30]张晓菲,赵长琦,刘丽宏.贫铀的危害及铀促排剂的研究进展[J].北京师范大学学报,2010,46(4):517-521.
[31]Mc Diarmid MA,Engelhardt SM,Dorsey CD,et al.Longitudinal health surveillance in a cohort of Gulf War veterans 18 years after first exposure to depleted uranium[J].J Toxicol Environ Health Part A,2011,74(10):678-691.doi:10.1080/15287394.2011.539138.
[32]Mc Diarmid MA,Engelhardt SM,Dorsey CD,et al.Surveillance results of depleted uranium-exposed Gulf War I veterans:sixteen years of follow-up[J].J Toxicol Environ Health Part A,2009,72(1):14-29.doi:10.1080/15287390802445400.