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目的探讨性成熟前期亚砷酸钠(NaAsO_2)染毒致雌性SD大鼠子宫、卵巢结构改变及性激素水平变化影响。方法 SD大鼠40只,随机分为4组,即对照组、低、中、高剂量砷组,分别灌胃给予双蒸水、1.25、2.50、5.00 mg/kg NaAsO_2,4周后,断颈处死,双侧卵巢及子宫做苏木素-伊红染色观察卵巢及子宫组织形态学变化;采用放射免疫法测定血清中卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇、孕酮含量;酶联免疫法检测血清中血管内皮生长因子(VEGF)、细胞周期蛋白D1(cyclin D1)、孕激素受体(PR)含量。结果随NaAsO_2剂量增加,染砷组大鼠卵巢内总卵泡数减少、细胞发育不良、成熟卵泡减少及畸形发育;子宫内膜变薄,腺体减少,腺腔变窄,腺上皮细胞由长柱状变成短柱状,间质增宽;与对照组比较,中、高剂量砷组大鼠血清中FSH、LH、雌二醇含量[分别为(3.23±0.20)、(3.21±0.18)IU/L、(2.64±0.27)、(2.62±0.25)ng/m L、(56.69±6.37)、(55.95±7.25)pg/m L]明显下降,差异有统计学意义(P<0.05);与对照组比较,中、高剂量砷组大鼠血清中VEGF、cyclin D1、PR蛋白含量[分别为(13.54±1.98)、(12.44±2.06)ng/L、(1.089±0.133)、(1.040±0.136)μg/L、(324.27±19.77)、(320.46±18.01)ng/L]下降,差异有统计学意义(P<0.05)。结论性成熟前期染毒NaAsO_2可引起SD雌性大鼠卵巢与子宫结构改变,其机制可能与NaAsO_2导致大鼠雌二醇水平下降,下丘脑分泌FSH、LH减少有关。
Objective To investigate the changes of uterus and ovary and sex hormone levels in female SD rats exposed to sodium arsenite (NaAsO_2) during sexual precanceration. Methods Forty Sprague-Dawley rats were randomly divided into 4 groups: control group, low, medium and high dose arsenic group. The rats were drenched with double distilled water, 1.25, 2.50 and 5.00 mg / kg NaAsO 2 respectively, The ovaries and uterus were hematoxylin-eosin (HUVEC) stained with ovaries and uterus to observe the morphological changes of ovary and uterus. The contents of FSH, LH, estradiol and progesterone in serum were determined by radioimmunoassay Serum levels of vascular endothelial growth factor (VEGF), cyclin D1 and progesterone receptor (PR) were detected by enzyme-linked immunosorbent assay. Results With the increase of NaAsO 2 dose, the total number of ovarian follicles in the arsenic-treated rats decreased, the cells developed poorly, the mature follicles decreased and the deformity developed. The endometrium became thinner, the glands reduced and the glandular cavity narrowed. The glandular epithelial cells consisted of long columnar (3.23 ± 0.20) and (3.21 ± 0.18) IU / L respectively in the middle and high dose arsenic group compared with the control group , (2.64 ± 0.27), (2.62 ± 0.25) ng / m L, (56.69 ± 6.37) and (55.95 ± 7.25) pg / m L respectively. There was significant difference between the two groups The contents of VEGF, cyclin D1 and PR in the serum of rats in the arsenic group were (13.54 ± 1.98), (12.44 ± 2.06) ng / L, (1.089 ± 0.133) and (1.040 ± 0.136) μg /L,(324.27 ± 19.77),(320.46 ± 18.01)ng/L], the difference was statistically significant (P <0.05). Conclusions NaAsO 2 can induce ovarian and uterine structures in female SD rats prematurely, and its mechanism may be related to the decrease of estradiol level and the secretion of FSH and LH in hypothalamus induced by NaAsO 2.