大鼠砷暴露致雌激素效应及对甲状腺功能的影响

目的 探讨大鼠砷暴露和雌激素受体(estrogen receptor α, ERα)抑制剂干预后,对雌激素及其受体和甲状腺相关激素及受体的影响,阐释砷的甲状腺毒性作用途径。 方法 大鼠亚砷酸钠饮水染毒,并给予雌激素受体抑制剂(ICI182780)干预。通过ELISA检测大鼠血清雌二醇(estradiol, E2)、总三碘甲状腺原氨酸(total triiodothyronine, TT3)、总甲状腺素(total thyroxine, TT4)、促甲状腺激素(thyroid stimulating hormone, TSH)水平;透射电镜观察大鼠甲状腺组织病理形态学结构改变;实时荧光定量法检测甲状腺组织ERα、甲状腺激素受体α(thyroid hormone receptor α, TRα)相对表达量。蛋白免疫印迹法检测甲状腺组织TRα蛋白水平。 结果 砷暴露后雌性大鼠E2表达水平较对照组上升(P<0.05),雌雄大鼠低砷组ERα、TRα相对表达量较对照组均下降(P<0.05)。高剂量砷暴露后雌性大鼠TSH、TT3及TRα表达水平较对照组上升,TT4较对照组下降(P<0.05)。ICI182780可降低雌性大鼠E2表达水平的上升,也对砷暴露大鼠TT4、TSH、ERα、TRα表达的改变有反向调节作用(P<0.05)。 结论 低砷暴露对雌性大鼠有明显的雌激素效应,高砷暴露可造成大鼠甲状腺功能紊乱或损伤。ERα可能是体内砷暴露发挥雌激素效应的主要途径之一。ICI182780可拮抗砷暴露导致的雌激素效应并缓解甲状腺功能的损伤。

Estrogenic effect of arsenic exposure and its effect on thyroid function in rats

Objective To explore the effects of arsenic exposure and estrogen receptor inhibitor on estrogen and its receptor and thyroid hormone receptor in rats, and to explain the pathway of thyroid toxicity of arsenic. Methods Rats drank water with sodium arsenite, and then were given estrogen receptor inhibitor (ICI182780) intervention. The levels of serum estradiol (E2), total triiodothyronine (TT3), total thyroxine (TT4) and thyroid stimulating hormone (TSH) in rats were detected by enzyme linked immunosorbent assay. Transmission electron microscope was used to observe thyroid histopathological structure changes in rats. Quantitative real-time polymerase chain reaction was employed to detect relative expression of thyroid tissue oestrogen receptor α (ERα) and thyroid hormone receptor α (TRα).TRα protein level in thyroid tissue was detected by western blot. Results After arsenic exposure, the level of E2 expression in female rats increased compared with the control group (P<0.05), but the relative expression of ERα and TRα in male and female rats of the low-arsenic group decreased compared with the control group (P<0.05). After high-dose arsenic exposure, the levels of TSH, TT3 and TRα expression in female rats increased compared with the control group, but the level of TT4 expression decreased compared with the control group (P<0.05). ICI182780 could reduce the increase in E2 expression level in female rats and also had a reverse regulation for changes in TT4, TSH, ERα and TRα expression in arsenic-exposed rats (P<0.05). Conclusion Low-arsenic exposure has a significant estrogen effect on female rats, and high-arsenic exposure can cause thyroid dysfunction or damage in rats. ERα may be one of the main ways for arsenic exposure to exert estrogen effects in the body. ICI182780 can antagonize estrogen effects caused by arsenic exposure and relieve damage to thyroid function.