砷染毒对大鼠雌激素及其受体的影响

Effects of Arsenic on Estrogen and Its Receptor in Rats

[目的]探讨砷染毒对大鼠雌激素及其受体的影响和雌激素受体(ER)信号通路指标间的关系。[方法]以雌性SD大鼠为实验动物,随机分成4组,每组6只。用亚砷酸钠灌胃染毒。分别为:对照组、低砷组(0.625 mg/kg)、中砷组(2.500 mg/kg)、高砷组(10.000 mg/kg)。每天1次灌胃染毒,连续3个月。染毒结束用酶联免疫吸附法测定大鼠血清中卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E2)及ER的水平。[结果]对照组、低砷组、中砷组、高砷组FSH表达水平分别为:(26.05±2.10)、(18.23±1.58)、(10.22±1.58)、(2.07±0.79)IU/L;LH表达水平分别为:(39.43±1.65)、(10.33±2.08)、(1.95±0.29)、(0.60±0.23)IU/L;E2表达水平分别为:(54.92±5.14)、(40.68±3.01)、(9.20±1.92)、(9.03±1.02)ng/L;ER表达水平分别为:(41.06±2.14)、(24.32±2.21)、(22.16±3.16)、(9.06±2.06)ng/L。随着砷染毒剂量的增高,FSH、LH表达逐渐降低(P<0.01);除E2在砷中、高染毒剂量(2.500、10.000 mg/kg),ER在砷低、中染毒剂量(0.625、2.500 mg/kg)的表达水平差异无统计学意义(P>0.05)外,其余剂量间表达差异均有统计学意义(P<0.01)。尿砷与FSH、LH、E2、ER间存在剂量-效应关系,砷、尿砷与FSH、LH、E2、ER均为负相关关系(P<0.05);ER信号通路指标间FSH、LH与E2,E2与ER间均为正相关关系(P<0.05)。[结论]雌激素及其受体参与了砷暴露致大鼠生殖系统的损伤,砷抑制ER通路各指标的表达,砷很可能是内分泌干扰物。

[ Objective ] To examine the effects of arsenic on estrogen and its receptor as well as the relationships among the indicators of estrogen receptor （ER） signaling pathway in rats. [ Methods ] Female SD rats were divided into four groups with six rats each and were exposed to NaAsO2 （0, 0.625, 2.500, and lO.000mg/kg） by oral perfusion, once a day, for three consecutive months respectively. The concentrations of follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, estradiol （E2）, and ER in serum were determined by enzyme-linked immunosorbent assay. [ Results ] The levels of FSH in the control, low arsenic, middle arsenic, and high arsenic groups were （26.05 ±2.10）, （18.23 ± 1.58）, （10.22 ± 1.58）, and （2.07 ± 0.79） IU/L, respectively; the levels of LH were （39.43 ± 1.65）, （10.33 ± 2.08）, （1.95 ± 0.29）, and （0.60 ±0.23）IU/L, respectively; the levels of E2 were （54.92 ± 5.14）, （40.68 ± 3.01）, （9.20 ：t： 1.92）, and （9.03 ± 1.02） ng/L, respectively; the levels of ER were （41.06±＋ 2.14）, （24.32 ± 2.21）, （22.16 ± 3.16）, and （9.06 ±2.06）ng/L, respectively. With the increasing of arsenic, the expression levels of FSH and LH gradually decreased （P〈0.01）. The expression levels of E2 and ER were of significant differences between groups treated with different doses of arsenic （P〈0.01） except the E2 in the middle and high arsenic groups （2.500, 10.000mg/kg） and the ER in the low and middle arsenic groups （0.625, 2.500 mg/kg）. There were dose-effect relationships of arsenic exposure with FSH, LH, E2, and ER. Arsenic and urinary arsenic were negatively associated with FSH, LH, E2, and ER （P〈0.05）. E2 was positively associated with FSH, LH, and ER （P〈0.05）. [ Conclusion ] Estrogen and its receptor participate in the process of reproductive system damage caused by arsenic. The expression levels of the ER pathway indicators are inhibited by arsenic. Therefore, arsenic is probably an endocrine disrupting chemical.