低剂量亚慢性纳米氧化镍对雄性大鼠的生殖毒性的影响

目的 探讨低剂量亚慢性纳米氧化镍染毒致雄性SD大鼠生殖毒性的机制。方法 将50只雄性SD大鼠按体质重（180～220 g）采用随机数字表分为5组，生理盐水对照组、4 mg/mL Micro-NiO阳性对照组及0.16、0.8、4 mg/mL Nano-NiO,采用非暴露式气管滴注法染毒，1次/3d，60天后，检测大鼠睾丸组织氧化应激指标、凋亡相关靶基因及蛋白的表达。结果 与生理盐水对照组相比，0.8、4 mg/mL Nano-NiO组 SOD活力、CAT活力、GSH-Px活力，均下降（P<0.05）； MDA含量均升高（P<0.05）。与生理盐水对照组和0.16 mg/mL Nano-NiO组相比，0.8、4 mg/mL Nano-NiO组Bax、Caspase-3mRNA的表达水平和Bax/Bcl-2 mRNA表达比值均升高（P<0.05），而Bcl-2 mRNA表达水平均降低（P<0.05）；与生理盐水对照组和0.16 mg/mL Nano-NiO组相比，0.8、4 mg/mL组睾丸组织Bax、Caspase-3蛋白的表达水平均升高（P<0.05）；而0.8、4 mg/mL Nano-NiO组睾丸组织Bcl-2蛋白的表达水平均下降（P<0.05）。结论 0.8mg/L及以上浓度纳米氧化镍染毒60天可对雄性大鼠产生生殖毒性，Caspase-3和Bax基因和蛋白表达升高, Bcl-2表达下降，这可能是0.8mg/L及以上浓度纳米氧化镍染毒60天导致大鼠睾丸生殖细胞凋亡发生的重要途径

Effect of subchronic low-dose nano-nickel oxide on reproductive toxicity in male rats

To investigate the mechanism of reproductive toxicity of male SD rats induced by low-dose subchronic nanometer nickel oxide. Methods 50 male SD rats were divided into five groups according to their body weight(180-220 g) using a random number table. Included a saline control group, a 4 mg/mL Micro-NiO positive control group, and 0.16, 0.8, and 4 mg/mL Nano-NiO groups. The rats were exposed to non-exposed tracheal instillation, once every 3 days. After 60 days, the expressions of oxidative stress indicators, apoptosis-related target genes and proteins in rat testicular tissues were detected. Results Compared with the normal saline control group, the SOD activity, CAT activity, and GSH-Px activity of the 0.8 and 4 mg/mL Nano-NiO groups all decreased(P<0.05), the MDA contents increased(P<0.05). Compared with the normal saline control group and the 0.16 mg/mL Nano-NiO group, the expression levels of Bax, Caspase-3 mRNA and Bax/Bcl-2 mRNA in the 0.8-and 4 mg/mL Nano-NiO groups were all increased(P< 0.05), and the Bcl-2 mRNA expression level decreased(P<0.05). Compared with the normal saline control group and the 0.16 mg/mL Nano-NiO group, the expression level of Bax and Caspase-3 protein in the testicular tissues of the 0.8 and 4 mg/mL groups, increased(P<0.05) while the expression level of Bcl-2 protein in the testis tissue of the Nano-NiO group at 0.8 and 4 mg/mL decreased(P<0.05). Conclusion Exposure to nanometer nickel oxide of 0.8 mg/L and above for 60 days can produce reproductive toxicity in male rats. The expressions of Caspase-3 and Bax genes and proteins are increased, and the expression of Bcl-2 is decreased. An important way for the testicular germ cell apoptosis in rats after exposure to nano-nickel oxide at the above concentration for 60 days.