宫内至出生早期DEHP暴露对大鼠甲状腺的毒性作用
首发时间:2019-04-11
摘要:目的:探讨宫内至出生早期DEHP暴露对大鼠甲状腺的毒性作用,为防治DEHP暴露对生命早期个体的毒性作用提供科学依据。方法:将受孕雌鼠分为4组,低、中、高三个剂量组的染毒剂量分别为0、5、50和250mg/kg/d;于GD 3天至F1代仔鼠断乳前(仔鼠出生后21天)给予F0代大鼠相应浓度的DEHP暴露;仔鼠出生后12周,称重处死后收集大鼠血清、甲状腺组织。采用放射免疫分析法测定血清中FT3、FT4、T3、T4、TSH水平; Western Blot法检测NIS、TPO、TG和Pax8蛋白水平。结果:与对照组相比,高剂量组雄性大鼠血清中T3、T4、FT4水平明显降低,差异有统计学意义(P<0.05);中剂量组雌性大鼠血清中组T3、FT3、T4和FT4水平显著降低,差异有统计学意义(P<0.05)。与对照组和低剂量组相比,雄性大鼠甲状腺NIS和TPO的蛋白表达水平增加,PAX8的蛋白表达水平下降,差异具有统计学意义(P<0.05);中剂量组雌性大鼠甲状腺NIS、TPO、TG和PAX8的蛋白表达水平均高与其它剂量组且差异具有统计学意义(P<0.05)。结论:DEHP可能通过母体暴露,影响子代甲状腺激素合成代谢相关酶和蛋白的表达,从而影响血清中甲状腺激素水平,导致甲状腺功能紊乱,产生甲状腺毒性作用。
关键词: 环境卫生学 DEHP 宫内暴露 甲状腺毒性 甲状腺激素
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Effects of DEHP Exposure on Thyroid of SD Rats from Intrauterine to Early Birth
Abstract:Abstract: Objective: Investigate the toxic mechanism of DEHP exposure to thyroid glands of SD rats from the intrauterine to the early birth and provide a scientific basis for prevention and treatment of the effects of DEHP exposure on early life individuals. Methods: the pregnant female rats were divided into 4 groups and the treatment doses were 0, 5, 50, 250 mg/kg/d. The rats in the F0 generation were exposed to DEHP from GD0 to PND21. 6 weeks after their birth, rats were weighted and then killed to collect the serum and thyroid. The levels of FT3, FT4, T3, T4 and TSH in serum were determined by radioimmunoassay. Western blot was used to detect NIS. , TPO, TG, Pax8 protein expression. Result: Compared with the control group, the levels of T3, T4 and FT4 in the serum of the high-dose group were significantly lower (P<0.05). The levels of T3, FT3, T4 and FT4 in the serum of the female rats in the middle dose group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the control group and the low-dose group, the protein expression levels of thyroid NIS and TPO in male rats increased, and the protein expression level of PAX8 decreased, the differences were statistically significant (P<0.05). The protein expression levels of thyroid NIS, TPO, TG and PAX8 in the middle dose group were significantly higher than those in the other dose groups (P<0.05).Conclusion: DEHP can affect the expression levels of thyroid hormone anabolism-related enzymes and proteins of the Offspring rats which result in the expression of thyroid hormones in the serum, and cause the thyroid toxicity through maternal exposure.
Keywords: Environmental Health DEHP intrauterine exposure toxicity of thyroid thyroid hormone
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宫内至出生早期DEHP暴露对大鼠甲状腺的毒性作用
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