纳米TiO_2对子代大鼠免疫系统的毒性研究
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摘要
目的:研究纳米二氧化钛(nano-TiO_2)对子代大鼠免疫系统的毒性。方法:实验分为nano-TiO_2组和对照组,每组45只SD大鼠(雌鼠30只、雄鼠15只)。染毒组每天给予250 mg/kg的nano-TiO_2混悬液,对照组每天灌胃给予等体积生理盐水,灌胃2周后进行交配,各组雌鼠在交配期、妊娠期、哺乳期继续灌胃染毒。F1代子鼠从离乳到处死持续灌胃染毒。在子鼠出生后第56天进行免疫毒性评价,指标包括免疫器官(肝、脾和胸腺)脏器系数、脾和潘氏淋巴结淋巴细胞分型、脾抗体生成细胞检测。结果:与对照组比较,nano-TiO_2组F1代雌鼠脾脏系数升高,而雄鼠肝脏系数降低,差异均有统计学意义(P均<0.05),但病理学检查未发现异常;淋巴细胞分型和抗体生成细胞试验结果的差异均无统计学意义(P均>0.05)。结论:在本试验条件下,Nano-TiO_2对F1代子鼠免疫系统功能未见明显不良影响。
OBJECTIVE:To explore the effects from exposure to nano-TiO_2 on the immune system ofoffspring of rats.METHODS:SD rats were divided into nano-TiO_2 and control groups with 30 females and15 males in each group.Exposed groups were given nano-TiO_2 by gastric filling method at the doses of 250mg/kg,and the control group was given equal volume of NaCl.The exposure was continued for 2 weeks beforemating,and throughout pregnancy and lactation.Offspring were infused nano-TiO_2 or NaCl into stomach fromweaning to execution.Immune function of offspring was observed on PND56.Observation indexes includedorgan coefficients of liver,spleen and thymus,and splenic and paneth lymphocyte typing and antibody-producing cell assay.RUSULTS:Organ coefficients of spleen in the nano-TiO_2 treated female rats group weresignificantly higher than that of the control group(P<0.05).Organ coefficients of liver in nano-TiO_2 treatedmale rats group were significantly lower than that of the control group(P<0.05).However,no abnormalitieswere found in histopathological examinations.No differences were observed on lymphocyte typing and antibody-producing cell assays between the nano-TiO_2 and the control groups(P>0.05).CONCLUSION:The resultsuggests that,under the present experimental conditions,nano-TiO_2 has no effect on the immune system ofoffspring of rats.
OBJECTIVE:To explore the effects from exposure to nano-TiO_2 on the immune system ofoffspring of rats.METHODS:SD rats were divided into nano-TiO_2 and control groups with 30 females and15 males in each group.Exposed groups were given nano-TiO_2 by gastric filling method at the doses of 250mg/kg,and the control group was given equal volume of NaCl.The exposure was continued for 2 weeks beforemating,and throughout pregnancy and lactation.Offspring were infused nano-TiO_2 or NaCl into stomach fromweaning to execution.Immune function of offspring was observed on PND56.Observation indexes includedorgan coefficients of liver,spleen and thymus,and splenic and paneth lymphocyte typing and antibody-producing cell assay.RUSULTS:Organ coefficients of spleen in the nano-TiO_2 treated female rats group weresignificantly higher than that of the control group(P<0.05).Organ coefficients of liver in nano-TiO_2 treatedmale rats group were significantly lower than that of the control group(P<0.05).However,no abnormalitieswere found in histopathological examinations.No differences were observed on lymphocyte typing and antibody-producing cell assays between the nano-TiO_2 and the control groups(P>0.05).CONCLUSION:The resultsuggests that,under the present experimental conditions,nano-TiO_2 has no effect on the immune system ofoffspring of rats.
引文
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[5]林本成,袭著革,张英鸽.应用流式细胞分析技术研究微纳尺度SiO2对雄性大鼠睾丸生精细胞的毒性作用[J].生态毒理学报,2007,2(3):193-198.
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[7]邵政,杨林,黄楚楚,等.纳米二氧化钛对小鼠生殖毒性的研究进展[J].中国药理学与毒理学杂志,2015,29(3):503-506.
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[12]付艳云,张艳秋,马书梅,等.纳米二氧化钛对大鼠NK细胞活性和相关细胞因子的影响[J].癌变·畸变·突变,2014,26(3):161-164.
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[14]周勇,刘瑜,何军山,等.纳米级铅对小鼠免疫球蛋白和T淋巴细胞亚型影响的研究[J].实用预防医学,2015,22(7):781-782.
[15]丁小波,文利新,牛同利,等.纳米氧化锌对小鼠免疫功能的影响[J].饲料研究,2007,9:1-4.
[16]王晶,洪铁,张英鸽.纳米粒子对免疫系统的影响[J].中国药理学与毒理学杂志,2012,26(2):242-246.
[17]徐一凡,支媛,汪会玲,等.重组人乳铁蛋白对子代大鼠免疫功能影响的一代繁殖毒性扩展试验[J].中国食品卫生杂志,2016,28(2):155-159.
[18]司少艳,王宗烨,吕广明,等.纳米氧化铈对X射线照射小鼠外周血免疫细胞分布及脾脏T淋巴细胞增殖能力的影响[J].中华放射医学与防护杂志,2017,37(5):339-344.
[19]FU Y,ZHANG Y,CHANG X,et al.Systemic immune effects of titanium dioxide nanoparticles after repeated intratracheal instillation in rat[J].Int J Mol Sci,2014,15(4):6961-6973.
[20]WANG X,PODILA R,SHANNAHAN J H,et al.Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2inflammatory responses via the IL-33/ST2 axis[J].Int JNanomed,2013,8:1733-1748.
[21]PARK E J,YOON J,CHOI K,et al.Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation[J].Toxicology,2009,260(1/2/3):37-46.
[22]SANG X,ZHENG L,SUN Q,et al.The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles[J].J Biomed Mater Res,2012,100(4):894-902.
[23]曾文婷,卢雪梅,汪洁,等.肝靶向干扰素对小鼠免疫毒性的初步研究[J].中国生化药物杂志,2015,35(4):45-47.
[2]HONG F,ZHOU Y,ZHAO X,et al.Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice[J].Int J Nanomed,2017,12:6197-6204.
[3]刘晓闰,唐萌.纳米二氧化钛的毒性研究与安全性展望[J].东南大学学报,2011,30(6):945-952.
[4]吕颖,方丽,胡巍.纳米颗粒与生物大分子的相互作用及其生物毒性机制[J].微生物免疫学进展,2012,40(4):82-85.
[5]林本成,袭著革,张英鸽.应用流式细胞分析技术研究微纳尺度SiO2对雄性大鼠睾丸生精细胞的毒性作用[J].生态毒理学报,2007,2(3):193-198.
[6]JIA X,WANG S,ZHOU L,et al.The potential liver,brain,and embryo toxicity of titanium dioxide nanoparticles on mice[J].Nanoscale Res Lett,2017,12(1):478.
[7]邵政,杨林,黄楚楚,等.纳米二氧化钛对小鼠生殖毒性的研究进展[J].中国药理学与毒理学杂志,2015,29(3):503-506.
[8]WEIR A,WESTERHOFF P,FABRICIUS L,et al.Titanium dioxide nanoparticles in food and personal care products[J].Environ Sci Technol,2012,46(4):2242-2250.
[9]RIEHEMANN K,SCHNEIDER S W,LUGER T A,et al.Nanomedicine-challenge and perspectives[J].Angew Chem Int Ed Eng,2009,48(5):872-897.
[10]LAURENCIN C T,KUMBAR S G,NUKAVARAPU S P.Nanotechnology and orthopedics:a personal perspective[J].Wiley Interdiscip Rev Nanomed Nanobiotechnol,2009,1(1):6-10.
[11]薛猛,朱融融,孙晓宇,等.纳米二氧化钛的发育毒性研究[J].材料导报,2009,23(4):103-105.
[12]付艳云,张艳秋,马书梅,等.纳米二氧化钛对大鼠NK细胞活性和相关细胞因子的影响[J].癌变·畸变·突变,2014,26(3):161-164.
[13]马艳菊,郁昂.纳米二氧化钛的毒性研究进展[J].环境科学与管理,2009,34(8):33-37.
[14]周勇,刘瑜,何军山,等.纳米级铅对小鼠免疫球蛋白和T淋巴细胞亚型影响的研究[J].实用预防医学,2015,22(7):781-782.
[15]丁小波,文利新,牛同利,等.纳米氧化锌对小鼠免疫功能的影响[J].饲料研究,2007,9:1-4.
[16]王晶,洪铁,张英鸽.纳米粒子对免疫系统的影响[J].中国药理学与毒理学杂志,2012,26(2):242-246.
[17]徐一凡,支媛,汪会玲,等.重组人乳铁蛋白对子代大鼠免疫功能影响的一代繁殖毒性扩展试验[J].中国食品卫生杂志,2016,28(2):155-159.
[18]司少艳,王宗烨,吕广明,等.纳米氧化铈对X射线照射小鼠外周血免疫细胞分布及脾脏T淋巴细胞增殖能力的影响[J].中华放射医学与防护杂志,2017,37(5):339-344.
[19]FU Y,ZHANG Y,CHANG X,et al.Systemic immune effects of titanium dioxide nanoparticles after repeated intratracheal instillation in rat[J].Int J Mol Sci,2014,15(4):6961-6973.
[20]WANG X,PODILA R,SHANNAHAN J H,et al.Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2inflammatory responses via the IL-33/ST2 axis[J].Int JNanomed,2013,8:1733-1748.
[21]PARK E J,YOON J,CHOI K,et al.Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation[J].Toxicology,2009,260(1/2/3):37-46.
[22]SANG X,ZHENG L,SUN Q,et al.The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles[J].J Biomed Mater Res,2012,100(4):894-902.
[23]曾文婷,卢雪梅,汪洁,等.肝靶向干扰素对小鼠免疫毒性的初步研究[J].中国生化药物杂志,2015,35(4):45-47.