砷中毒地区女性妊娠结局及生殖系统疾病 生物学标志物的研究

Pregnancy outcomes in different arsenic poisoning regions and biomarkers of female reproductive system injury

摘要:

目的 探讨不同砷中毒地区女性生殖系统损伤的生物标志物。方法 收集曲靖市不同砷暴露地区女 性的资料，将不同砷暴露地区的女性按照暴露剂量不同分为低砷暴露组和高砷暴露组，把非暴露地区的女性作 为对照组。采用氢化物发生- 原子吸收分光光度法测定尿液中和外周血中砷的含量。酶联免疫吸附试验检测血 中砷含量及雌激素水平。结果 生活在高砷地区的女性妊娠期出现妊娠期高血压和妊娠期不良妊娠结局的概率< 对照组，差异有统计学意义（P <0.05）；高砷地区的女性生殖系统肿瘤的发生率高于对照组，差异有统计学意义 （P <0.05）。随着砷暴露浓度增高，女性的血砷和尿砷呈增高的趋势，且存在剂量- 效应关系，砷暴露组女性体内 的血砷和尿砷高于对照组女性体内的水平，差异有统计学意义（P <0.05）。高砷暴露组和低砷暴露组女性体内的 雌二醇（E2）激素水平低于对照组女性体内水平，差异有统计学意义（P <0.05）；高砷暴露组和低砷暴露组女性 体内的孕激素（P4）、黄体生成素（LH）激素水平低于对照组女性体内激素水平，差异有统计学意义（P <0.05）。 不同水平的砷暴露影响女性性腺的雌激素受体的表达水平，在低砷暴露组和高砷暴露组女性的子宫和卵巢中发 生了雌激素受体（ER）、孕激素受体（PR）高表达的情况。结论 尿砷、血砷可以作为砷暴露地区女性生殖系 统损害的暴露标志物，E2、P4、LH、ER、PR 可作为效应标志物。

Abstract:

Objective To explore the biomarkers of female reproductive system damage in different arsenic poisoning areas. Methods The data of women exposed to arsenic in different areas of Qujing city were collected, According to different concentrations of arsenic exposure, the subjects were divided into a high-dose exposure group and a low-dose exposure group. The women in the unexposed areas were enrolled into the control group. The content of arsenic in urine and peripheral blood was determined by hydride generation-atomic absorption spectrophotometry. The levels of estrogen and progesterone in serum were determined by enzyme-linked immunosorbent assay. Results The women living in the high-arsenic-exposure areas were more likely to have gestational hypertension and adverse pregnancy outcomes than those in the non-arsenic-exposure areas (P < 0.05). The total incidence of the reproductive system tumors in the high-dose exposure group was also significantly higher than that in the control group (P < 0.05). With the increase of arsenic exposure concentration, the levels of blood arsenic and urine arsenic in the women tended to increase, and there was a dose-response relationship; the levels of blood arsenic and urine arsenic in the arsenic exposure groups were significantly higher than those in the control group (P < 0.05). The levels of estradiol (E2), progesterone (P4) and luteinizing hormone (LH) in the high-dose exposure group and the low-dose exposure group were significantly lower than those in the control group (P < 0.05). Different levels of arsenic exposure affected the expression level of estrogen receptor in female gonad. The high expressions of estrogen receptor (ER) and progesterone receptor (PR) were found in the uteruses and ovaries of the women in the low-dose exposure group and the high-dose exposure group. Conclusions Urinary arsenic and blood arsenic can be used as the exposure markers of the female reproductive system damage in arsenic-exposure areas, while E2, P4, LH, ER and PR can be used as markers of effect.