出生前邻苯二甲酸二(2-乙基己基)酯暴露对青春期雄性大鼠甲状腺激素合成的影响

Effects of prenatal exposure to di-(2-ethylhexyl) phthalate on thyroid hormones synthesisin adolescent male rats

目的探讨出生前邻苯二甲酸二(2-乙基己基)酯[di-(2-ethylhexyl)phthalate,DEHP]暴露对青春期雄性大鼠甲状腺激素合成的影响。方法将32只健康SPF级SD妊娠大鼠随机分为4组,分别为对照(玉米油)组和2、10、50 mg/kg DEHP染毒组,每组8只。于妊娠第14~19天,采用灌胃方式进行染毒,每日1次。子代大鼠于42日龄测定血清THs及TSH水平和甲状腺Tpo、Nis、Tg基因的表达水平。结果与对照组相比,10 mg/kg DEHP染毒组青春期雄性大鼠血清甲状腺素(T4)的水平和10、50 mg/kg DEHP染毒组血清总三碘甲腺原氨酸(T3)的水平均升高,而10、50 mg/kg DEHP染毒组青春期雄性大鼠血清TSH的水平均降低,差异均有统计学意义(P<0.01);且随着DEHP染毒剂量的升高,青春期雄性大鼠血清T4与T3的水平均呈先升高后下降的趋势,而血清TSH的水平呈下降趋势。与对照组相比,10、50 mg/kg DEHP染毒组青春期雄性大鼠甲状腺中Nis、Tg基因及50 mg/kg DEHP染毒组青春期雄性大鼠甲状腺中Tpo基因的表达水平均下调,差异均有统计学意义(P<0.05);且随着DEHP染毒剂量的升高,青春期雄性大鼠甲状腺中Tpo、Nis、Tg基因表达水平均呈下降趋势。结论出生前DEHP暴露可能通过干扰甲状腺激素合成相关基因的表达而影响甲状腺激素的合成,并干扰甲状腺的功能。

Objective To investigate the effects of prenatal di-(2-ethylhexyl)phthalate(DEHP)exposure on thyroid hormone synthesis in adolescent male rats.Methods A total of 32 healthy pregnant SD rats were randomly divided into four dose groups,eight in each.The pregnant rats were treated with corn oil(vehicle control),2,10 and 50 mg/kg DEHP respectively through gavage once a day from gestational day 14 to 19.At the age of 42 days,the levels of serum THs and TSH of the offspring rats were detected by Luminex liquid chip technology and the expression levels of three synthesis related genes,such as Tpo、Nis、Tg,in thyroid of the offspring rats was measured by real-time quantitative PCR.Results Compared with the control group,the level of serum T4 in the adolescent male rats in 10 mg/kg DEHP group and the level of serum T3 in the adolescent male rats in 10,50 mg/kg DEHP group were both increased,but the level of serum TSH in the adolescent male rats in 10,50 mg/kg DEHP group was decreased,the difference was statistically significant(P<O.01);Moreover,with the increase of DEHP exposure,the level of serum T4 and T3 in adolescent male rats increased first and then decreased,while the levels of serum TSH decreased.Compared with the control group,the expression levels of Nis and Tg genes in thyroid of adolescent male rats in 10 and 50 mg/kg DEHP groups and Tpo gene in thyroid of adolescent male rats in 50 mg/kg DEHP group were all down-regulated,with significant differences(P<0.05);Moreover,the expression levels of Tpo,Nis and Tg genes in thyroid of adolescent male rats decreased with the increase of DEHP exposure.Conclusion Prenatal DEHP exposure may affect the synthesis of thyroid hormone by interrupting the expression of genes related to thyroid hormone synthesis,as well as the function of thyroid in adolescent male rats.