目的采取不同剂量的亚砷酸钠(NaAsO_2)灌胃染毒,针对其对雌性SD大鼠性成熟前期ERmRNA(雌激素受体mRNA)的表达及VEGF(血管内皮生长因子)、Cyclin D_1(细胞周期蛋白D_1)和PR(孕激素受体)蛋白含量的影响,探讨其对生殖毒性的可能机制。方法 SD大鼠40只,随机分为4组:对照组、低剂量组、中剂量组和高剂量组,经灌胃,分别给予其双蒸水,1.25、2.5和5 mg/kg·d的NaAsO_2,4周后,断颈处死,取血、左侧卵巢做以下检测:(1)Elisa法测定VEGF、Cyclin D_1和PR蛋白的含量;(2)实时荧光定量PCR检测卵巢组织中ERmRNA的表达。结果 Elisa结果显示,随着灌胃的NaAsO_2剂量增加,中和高剂量大鼠血清VEGF、Cyclin D_1和PR蛋白含量分别为(13.54±1.98)ng/L、(12.44±2.06)ng/L、(1.089±0.133)μg/L、(1.040±0.136)μg/L、(324.27±19.77)ng/L和(320.46±18.01)ng/L呈下降趋势,中、高剂量组与对照组比较差异有统计学意义(P<0.05)。RT-PCR结果显示,大鼠卵巢ER mRNA基因的表达降低,且低、中和高剂量组与对照组比较差异有统计学意义(P<0.05)。结论染毒NaAsO_24周后可引起SD雌性大鼠卵巢与子宫结构改变,在性成熟前期染毒NaAsO_2,可能通过下调卵巢ER mRNA基因,使得ER下游的VEGF、Cyclin D1蛋白以及PR蛋白生成减少,最终导致卵泡发育异常,产生生殖毒性。 Objective To investigate the effect of NaAsO_2 on the expression of ER mRNA (estrogen receptor mRNA) and VEGF (vascular endothelial growth factor), Cyclin D_1 Cyclin D_1) and PR (progesterone receptor) protein content, to explore its possible mechanism of reproductive toxicity. Methods Forty Sprague-Dawley rats were randomly divided into 4 groups: control group, low dose group, middle dose group and high dose group. The rats were given distilled water at 1.25, 2.5 and 5 mg / kg · d After 4 weeks, the rats were sacrificed and their blood samples were collected. The left ovaries were assayed as follows: (1) The contents of VEGF, Cyclin D_1 and PR were determined by Elisa method; (2) The expression of ER mRNA in ovarian tissues was detected by real- . Results The results of Elisa showed that the contents of VEGF, Cyclin D_1 and PR in serum of medium and high dose groups were (13.54 ± 1.98) ng / L, (12.44 ± 2.06) ng / L, (1.089 ± 0.133) μg / L, (1.040 ± 0.136) μg / L, (324.27 ± 19.77) ng / L and (320.46 ± 18.01) ng / L respectively. There was statistical difference between the medium and high dose groups and the control group Significance (P <0.05). The results of RT-PCR showed that the mRNA expression of ER mRNA in ovary decreased, and there was significant difference between low, middle and high dose group and control group (P <0.05). Conclusion NaAsO_24 could induce ovarian and uterine structure changes in SD female rats. Exposure to NaAsO_2 at premature sexual maturation may reduce the expression of ERβ, Cyclin D1 and PR proteins in ER, Cause abnormal follicular development, resulting in reproductive toxicity.