氯化汞雌激素样作用及其机制的实验研究

目的评价氯化汞(HgCl2)的雌激素样作用及其作用机制.方法从体内和体外两个水平,观察不同浓度的HgCl2对MCF-7人乳腺癌细胞增殖作用、去卵巢SD大鼠子宫的诱导增生作用、过氧化物活力的变化及对雌激素结合雌激素受体的影响.结果 10-6～10-9 mol/L的HgCl2均可引起MCF-7人乳腺癌细胞增殖,10-7 mol/L的HgCl2使MCF-7人乳腺癌细胞增殖达最大.每天0.04、0.20及1.00 mg/kg连续3 d腹腔注射HgCl2能刺激大鼠子宫增生和过氧化物酶活力增加;但HgCl2不影响雌二醇(E2)与雌激素受体结合.结论 HgCl2可能通过雌激素受体介导而表现出雌激素样作用,但不与E2竞争结合雌激素受体.

Experimental study on the estrogen-like effect and mechanism of Mercury chloride

Objective To study the estrogen-like effect of mercury chloride and its mechanism. Methods Mercury chloride was selected to perform proliferation assay of MCF-7 human breast cancer cells, uterotrophic assay, assay of peroxidase activity and estrogen receptor of rat uterine binding assay. Results Mercury chloride could proliferate the MCF-7 cell. The maximal increase was at 10 -7 mol/L, which was 3.08 folds higher compared to the negative control group. The relative rate of the proliferation effect of mercury chloride was 59.8%, and the proliferation of MCF-7 cells was 0.01. This effect of proliferation could be blocked completely by a pure antigestrogen ICI 182.780. Mercury chloride could increased the weight of uterus of ovariectomized SD rats and the peroxidase activity of uterus at the levels of 0.04 mg/kg,0.20 mg/kg and 1.00 mg/kg by intraperitoneal injection for 3 days. Mercury chloride could not affect the binding of estrogen receptor(ER) and cstradiol(E 2). Conclusion Mercury chloride exhibited the estrogen-like effect through binding and activating ER, but it could not bind to ER by competing with E 2.