丙基硫脲嘧啶对去卵巢大鼠甲状腺干扰作用的时效关系研究
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陈浩 男 硕士生 研究方向为食品毒理学 E-mail:chenhao0725@126.com

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国家自然科学基金(81273081)


Study on time-effect of propylthiouracil thyroid disruption in ovariectomized rats
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    摘要:

    研究丙基硫脲嘧啶(PTU)对甲状腺干扰作用的敏感指标及其时间效应模式。方法 去卵巢大鼠随机分为3个给药组,分别给予5mg/kg BW的PTU连续灌胃4、8和12d,同时设手术对照组和假手术对照组,灌胃给予玉米油。测定指标包括血清T3、T4和 TSH,肝脏I型5′-脱碘酶和苹果酸酶活性,甲状腺组织病理学改变以及表皮胶质比。结果 与手术对照组相比,给药各组血清T3均降低(P<0.05),TSH均升高(P<0.05)。与手术对照组相比,4d组血清T4差异无统计学意义(P>0.05),而8和12d组T4降低(P<0.05)。血清T3和T4随给药时间增加而下降,血清TSH则随时间增加而升高。同手术对照组相比,给药各组Ⅰ型5′-脱碘酶活性均降低(P<0.05),苹果酸酶活性差异无统计学意义(P>0.05)。给药各组甲状腺滤泡间可见毛细血管充血,滤泡上皮不同程度增生,胶质减少,表皮胶质比均升高(P<0.05)。结论 血清甲状腺激素T3、T4和TSH,I型5′-脱碘酶活性,甲状腺表皮胶质比及病理学改变可作为评价甲状腺干扰作用的敏感指标;PTU干扰去卵巢大鼠的甲状腺功能存在明显的时效关系,给药8d是最敏感观察期。

    Abstract:

    To study thetime-effectmodel of PTU thyroid disruption and screen sensitive endpoints.MethodsOvariectomized rats were randomly allocated into 3groups, and propylthiouracil was administered at 5mg/kg BW by gavage for 4,8and 12days respectively. An OVX control and a sham control were also included in the study, treated with corn oil. At the end of the study, serum T3, T4and TSH levels, activities of liver type I 5′-deiodinase and malic enzyme were measured correspondingly. Histopathology of thyroid was described and thyroid follicular epithelium/colloid ratio was calculated. ResultsCompared with OVX control, animals treated with PTU showed significantly higher serum T3, and lower TSH levels, while only 8-day and 12-day groups had significantly lower serum T4levels. The activity of liver type Ⅰ 5′-deiodinase decreased significantly, while malic enzyme did not show any significant difference among the groups. Histopathology results revealed the hypertrophy of thyroid, disappearance of colloid, adding that the ratio of epithelium versus colloid increased significantly. ConclusionPTU could effectively affect the structure and function of thyroid with time-effect trend; thyroid hormone, type I 5′-deiodinase activity and histopathology endpoints were sensitive; 8-day treatment of thyroid disruptor had the optimal observation.

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陈浩,张晓鹏,李谦,苏卿,贾旭东,刘兆平.丙基硫脲嘧啶对去卵巢大鼠甲状腺干扰作用的时效关系研究[J].中国食品卫生杂志,2014,26(1):18-22.

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  • 收稿日期:2013-10-10
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  • 在线发布日期: 2014-03-04
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