孕前/孕期砷暴露致胎鼠先天性心脏异常的研究

Study on congenital cardiac anomalies induced by arsenic exposure before and during maternal pregnancy in fetal rats

目的探讨孕前／孕期砷暴露对大鼠胚胎心脏发育的影响。方法30～40日龄雌性SD大鼠32只，按体重随机分为对照组和低、中、高剂量组，每组8只，分别自由饮用含亚砷酸钠（NaAsO2）浓度为0、37．5、75和150mg／L的蒸馏水6周，与成年雄性SD大鼠合笼后受孕雌鼠继续饮用原浓度NaAsO2水溶液2周，孕16d剖腹取胎。观察雌鼠体重变化，流产、吸收胎数及胚胎生长发育情况；通过连续性切片、苏木素．伊红（HE）染色法光镜下观察胎鼠心脏形态结构；采用原子荧光光谱法检测雌鼠毛发砷含量。结果亚慢性砷暴露致雌鼠体重增长缓慢。中、高剂量组各有2只孕鼠流产。与对照组比较，染毒组胚胎重量、胎盘重量降低，吸收胎发生率升高（P〈0．05）。低、中、高剂量组可见胎鼠心脏畸形，包括室间隔缺损、房间隔缺损和法洛三联征。各组心脏畸形发生率随饮水砷浓度升高而升高，中、高剂量组与对照组比较差异均有统计学意义（P〈0．05）。各组雌鼠毛发砷含量随饮水砷浓度升高而升高（P〈0．01）。结论孕前／孕期砷暴露可致胎鼠心脏发育异常，增加先天性心脏病发病风险。

Objective To investigate the effects of arsenic exposure before and during maternal pregnancy on heart development of fetal rats. Methods According to body weight, thirty-two female SD rats （30 to 40 days of age） were randomly divided into control group, low dose group, middle dose group and high dose group with 8 rats per group. They were allowed free access to drinking water with 0, 37.5, 75 and 150 mg/L of sodium arsenite （NaAsO2） for 6 weeks, respectively. Then all the female rats and adult male SD rats were caged together for mating. Once female rats were determined to be pregnant, they would continue to drink deionized distilled water containing different concentrations of sodium arsenite for another 2 weeks. On embryonic day 16, rats were sacrificed to harvest fetuses. Female rats＇ weight changes, abortions, absorbed fetus number, growth and development of fetal rats were observed. Hematoxylin-eosin staining of serial cardiac slices was performed in embryos to observe cardiac morphology and structure. Fur arsenic contents of female rats were determined with the method of atomic fluorescence spectrometry. Results Subchronic arsenic exposure caused slow weight growth in female rats. There were two cases of abortion in middle dose group and high dose group, respectively. Compared with these of control group, fetal and placental weight decreased （ P 〈 O. 05）, and the incidence of fetal absorption increased （ P 〈 O. 05 ） in all arsenic-treated groups. Cardiac malformations in fetal rats including ventricular septal defect, atrial septal defect and tetralogy of Fallot were observed in low, middle and high dose group. The incidence of cardiac malformations increased with the increase of arsenic concentrations in drinking water. Compared with that of control group, the incidence of cardiac malformations remarkably increased in both middle and high dose groups （P 〈 O. 05）. Fur arsenic contents increased with the increase of arsenic concentrations in drinking water （P 〈 0. 01 ）. Conclusion Arsenic exposure before and during maternal pregnancy could cause abnormal cardiac development in fetal rats, and increased the risk of congenital heart disease.