三种典型纳米颗粒物对雄性大鼠的生殖毒性

Comparative study on effects of three kinds of typical nano particles on reproductive toxicity of male rats

目的探讨二氧化硅纳米颗粒(Si O_2NPs)、二氧化钛纳米颗粒(Ti O_2NPs)、四氧化三铁纳米颗粒(Fe_3O_4NPs)对雄性大鼠的生殖毒性效应。方法将80只健康SPF级雄性SD大鼠随机分为10组,分别为对照(生理盐水)组和1.5、4.5、13.5mg/kg Si O_2NPs、Ti O_2NPs、Fe_3O_4NPs染毒组,每组8只。采用非暴露气管插管滴注法进行染毒,染毒容积为1.0 ml/kg,隔日染毒1次,连续染毒4周。检测大鼠睾丸组织中乳酸脱氢酶同工酶-C4(LDH-C4)、琥珀酸脱氢酶(SDH)活力和睾酮(T)含量以及附睾精子数量、精子存活率、精子畸形率。结果与对照组相比,4.5、13.5 mg/kg Si O_2NPs、Ti O_2NPs和Fe_3O_4NPs染毒组大鼠的精子数量和精子存活率均降低,而精子畸形率均升高,差异有统计学意义(P<0.05);且随着Si O_2NPs、Ti O_2NPs和Fe_3O_4NPs染毒浓度的升高,大鼠精子数量和精子存活率均呈下降趋势,精子畸形率均呈上升趋势。与相同浓度的Si O_2NPs染毒组比较,13.5 mg/kg Ti O_2NPs染毒组大鼠的精子数量、精子存活率降低,而精子畸形率升高,差异均有统计学意义(P<0.05);另外,13.5 mg/kg Ti O_2NPs染毒组大鼠的精子畸形率高于相同浓度的Fe_3O_4NPs染毒组,差异有统计学意义(P<0.05)。与对照组相比,13.5 mg/kg Si O_2NPs、Ti O_2NPs、Fe_3O_4NPs染毒组大鼠睾丸LDH-C4、SDH的活力及4.5、13.5 mg/kg Si O_2NPs、Ti O_2NPs、Fe_3O_4NPs染毒组大鼠睾丸的T含量均降低,差异有统计学意义(P<0.05);且随着Si O_2NPs、Ti O_2NPs和Fe_3O_4NPs染毒浓度的升高,大鼠睾丸LDH-C4、SDH活力和T含量均呈下降趋势。与相同浓度的Si O_2NPs染毒组比较,13.5 mg/kg Ti O_2NPs染毒组大鼠睾丸的LDH-C4活力和T含量均降低,差异有统计学意义(P<0.05);13.5 mg/kg Ti O_2NPs染毒组大鼠睾丸T含量低于相同浓度的Fe_3O_4NPs染毒组,差异有统计学意义(P<0.05)。结论Si O_2NPs、Ti O_2NPs、Fe_3O_4NPs均可通过影响生殖系统关键酶和性激素水平引起大鼠的生殖毒性效应,且三种纳米颗粒物对大鼠的生殖毒性效应存在差异,以Ti O_2NPs最强。

Objective To compare the effects of silica nano particles （SiO2NPs）, titanium dioxide nano particles （TiO2NPs） and magnetic nano particles （Fe3O4NPs） on reproductive toxicity of male rats. Methods Eighty SD male rats were randomly divided into nine exposure groups and one control group,eight rats in each group. The rats in exposure groups were exposed to SiO2NPs,TiO2NPs, Fe3O4NPs at the doses of 1.5, 4.5 and 13.5 mg/kg body weight respectively by tracheal instillation while the control group were injected with normal saline once every other day. Four weeks later,the sperm deformity rate,the count and quality of sperm in epididymis,the content of testosterone （T）,the activities of succinate dehydrogenase （SDH） and lactate dehydrogenase isoenzyme-C4 （LDH-C4） in testis were examined. Results Compared with the control group,the sperm counts and the survival rates of spermatozoa were lower and the sperm deformity rate were significantly higher （P〈0.05） in SiO2NPs, TiO2NPs,Fe3O4Ps exposure groups at 4.5 and 13.5 mg/kg body weight, with a trend of dose dependent. Compared with the same concentration group of SiO2NPs, the sperm count and survival rate of spermatozoa were lower and the sperm deformity rate in 13.5 mg/kg body weight TiO2NPs exposure groups was significantly higher （P〈0.05）. In addition,the sperm deformity rate in 13.5 mg/kg body weight TiO2NPs exposure groups was higher than that of the same concentration group of Fe3O4NPs （P〈0.05）. Compared with the control group,the activities of SDH and LDH-C4 in 13.5 mg/kg body weight SiO2NPs,TiO2NPs and Fe3O4NPs exposure groups were significantly lower（P〈0.05）,and the contents of T in 4.5 and 13.5 mg/kg body weight SiO2NPs, TiO2NPs, Fe3O4NPs exposure groups were significantly lower （P〈0.05）, and the content of T,the activities of SDH and LDH-C4 showed downward trends with the increases of the concentrations of SiO2NPs,TiO2NPs and Fe304NPs. Compared with 13.5 mg/kg body weight SiO2NPs group,the content of T and the activity of LDH-C4 in TiO2NPs exposure group at the same exposure level were lower （P〈0.05）; The content of T in 13.5 mg/kg body weight TiO2NPs exposure group was lower than that in Fe3O4NPs group at the same exposure level （P〈0.05）. Conclusion SiO2NPs,TiOzNPs and Fe3O4NPs have adverse effect on key enzymes and sex hormones of the reproductive system, which may induce reproductive toxicity to rats, and the reproductive toxicity of TiO2NPs is the highest.