有机磷阻燃剂TDCIPP对雌性大鼠甲状腺的潜在毒性作用

目的: 研究磷酸三(1, 3-二氯-2-丙基)酯(TDCIPP)对雌性大鼠甲状腺系统的潜在毒性作用及机制。方法: 将32只离乳3周的雌性SD大鼠随机分为对照组(玉米油灌胃)及TDCIPP低、中、高剂量组(50、100、250 mg/kg·d,溶于玉米油)(n=8),灌胃给药21 d,每天1次。于末次给药后处死动物,取血和甲状腺、肝脏,检测血清中促甲状腺激素(TSH)、三碘甲腺原氨酸(T3), 甲状腺素(T4)和游离甲状腺素(FT4)水平变化;组织切片(HE染色)用于检测甲状腺形态学病变;RT-PCR技术与Western blot技术检测与甲状腺功能相关的基因和蛋白表达的变化。结果: 与对照组比较,TDCIPP染毒后大鼠甲状腺出现滤泡排列不规则、胶质变少、滤泡增生、肥大等现象,TDCIPP低剂量组的血清TSH水平和高剂量组的T3水平均显著升高(P＜0.05),低剂量组促甲状腺激素受体(TSHR)mRNA表达和中、高剂量组甲状腺激素受体β(TRβ)蛋白表达均显著降低(P＜0.05,P＜0.01),中、高剂量组甲状腺过氧化物酶(TPO)mRNA表达显著增高(P＜0.05,P＜0.01),三个剂量组尿苷二磷酸葡萄糖醛酸转移酶(UGTs)、细胞色素氧化酶-3A1(CYP3A1)蛋白表达水平显著上调(P＜0.05)。结论: 大鼠暴露在50 mg/(kg·d)以上剂量的TDCIPP,即可以刺激甲状腺组织的增生,改变血清中甲状腺素的水平,干扰甲状腺的功能,表现出对甲状腺的毒性作用。

Potential toxic effects of TDCIPP on the thyroid in female SD rats

Objective: To investigate the potential toxic effects and mechanisms of Tris(1; 3-dichloro-2-propyl) phosphate (TDCIPP) on thyroid in female SD rats.Methods: Thirty-two 3-weeks-old female SD rats were randomly divided into normal group(treated with corn oil ), and low/moderate/high-dose group treated with TDCIPP (dissolved in corn oil )(n=8). All rats were treated with corn oil or TDCIPP (50, 100, 250 mg/(kg·d)) once a day during a 21-day period. All rats were sacrificed after the last administration. Serum thyroid stimulating hormone (TSH), 3,3’,5-triiodothyronine (T3), 3,3’,5,5’-tetraiodothyronine (T4), free 3,3’,5,5’-tetraiodothyronine (FT4) were detected with ELISA kit. Morphology of thyroid was observed with hematoxylin and eosin (HE) staining. Expressions of genes and proteins correlate with thyroid were measured respectively by real-time fluorescence quantitative PCR and Western blot. Results: Compared with control group, morphology of thyroid showed follicles irregular arrangement, hypocolloid, and follicular hyperplasia in TDCIPP treatment groups. The levels of serum TSH in low-dose TDCIPP group and T3 in high-dose TDCIPP group were significantly higher than those in control group(P＜0.05). Thyroid stimulating hormone receptor (TSHR) mRNA expression was decreased distinctly in low-dose TDCIPP group, while the expression of thyroperoxidase (TPO) mRNA was increased notably in moderate and high-dose TDCIPP groups(P＜0.05,P＜0.01). Compared with control group, the level of TRβ protein was decreased significantly in moderate and high-dose TDCIPP groups, while the expressions of udp-glucuronosyl-transferases (UGTs) and cytochrome-p450-3A1 (CYP3A1) proteins were upregulated notably in TDCIPP treatment groups(P＜0.05). Conclusion: Treated with 50 mg/(kg·d) TDCIPP can cause thyroid hyperplasia, change the levels of thyroid hormones, and disturb thyroid function, therefore, it has toxic effects on the thyroid.