高氯酸铵对去卵巢大鼠甲状腺干扰作用的研究  

The effects of ammonium perchlorate on thyroid function in ovariectomization rats

作　　者：毛伟峰[1] 陈浩[1] 包汇慧[1] 宋雁[1] 隋海霞[1] 刘兆平[1] 

机构地区：[1]国家食品安全风险评估中心/卫生部食品安全风险评估重点实验室,北京100022

出　　处：《毒理学杂志》2016年第2期91-95,96,共6页Journal of Toxicology

基　　金：国家自然科学基金(81273081)

摘　　要：目的研究高氯酸铵(Ammonium Perchlorate,AP)对去卵巢大鼠(ovariectomization,OVX)甲状腺干扰作用的剂量-反应关系,获得其有害作用的最小剂量(LOAEL)值和BMDL10值。方法 60只雌性SD大鼠随机分为假手术(SHAM)对照组、OVX对照组和4个AP处理组(剂量为50、100、250和500 mg/kg·bw),连续灌胃8 d。灌胃结束次日检测大鼠肝脏Ⅰ型5’-脱碘酶(5’-DI)活性、血清3’-三碘甲腺原氨酶(T3)、甲状腺素(T4)和促甲状腺激素(TSH)水平,观察甲状腺组织病理学、甲状腺脏器系数和甲状腺表皮/胶质比等。分析获得未观察到有害作用剂量(NOAEL)和观察到有害作用的最小剂量(LOAEL),以及采用基准剂量法获得基准剂量(BMD)的可信区间下限(BMDL)。结果 OVX组体重和增重均显著高于SHAM对照组(P<0.01),OVX各组间大鼠体重差异无统计学意义(P>0.05)。AP各剂量组血清T4、TSH、甲状腺脏器系数和表皮/胶质比的改变均有统计学意义(P<0.05),而5’-DI酶活性的改变均无统计学意义(P>0.05);250和500 mg/kg·bw剂量组的血清T3显著低于OVX对照组(P<0.01)。AP各剂量组甲状腺均出现不同程度的组织病理学损伤。AP对OVX大鼠血清T3、T4和TSH水平、甲状腺脏器系数和甲状腺表皮/胶质比的影响的LOAEL均为50 mg/kg·bw,AP对甲状腺干扰作用的BMDL10为15 mg/kg·bw。结论 AP对OVX大鼠甲状腺干扰作用呈显著的剂量-反应关系。AP对去卵巢大鼠甲状腺干扰作用的LOAEL为50 mg/kg·bw,BMDL10为15 mg/kg·bw。Objective To study the dose-response relationship of AP on thyroid function in ovariectomizationrats（OVX） and acquire the toxicological reference points. Methods Sixty SD rats were randomly allocated into six groups： SHAM control, OVX control, AP 4 groups （50, 100, 250 and 500 mg/kg, bw）. All dosed groups were treated with different dose of AP accordinglyand controls were treated with water for 8 consecutive days. Endpoints examined include serum T3, T4 and TSH, liver 5＇-DI activity, thyroid organ/body weight ratio, epithelium/collid ratio. NOAEL/LOAEL values were analysed based on the experiment data. BMDS was employed to analyze dose-response relationships and generate BMD and BMDL. Results Body weight of rats in OVX groups was significantly higher than that in shame control （P 〈 0. 01 ） and no significance of body weight change was observed among OVX groups. All AP treated groups showed significant changes in serum T4, TSH, thyroid/body weight ratio, and epithelium/colloid ratio （ P 〈 0. 05 ） , while no significant change in 5 ＇ -DI activity. Only AP 250 and 500 mg/kg, bw groups showed significant lower serum T3 levels compared with OVX control （P 〈 0. 05 ）. In all AP treated groups, different levels of thyroidhistopathological changes could be observed. For all endpoints, the LOAELs were observed, which was 50 mg/kg.bw. In the view of BMD, BMDL10 was 15 mg/kg.bw. Conclusions AP affect thyroid function of OVX rats with significant doseresponse relationship. The LOAELs is 50 mg/kg.bw, and the BMDL 10 is 15 mg/kg·bw for AP on thyroid function in OVX rats.

关 键 词：高氯酸铵 甲状腺干扰物 剂量-反应关系 毒理学参考点 基准剂量 

分 类 号：R995[医药卫生—毒理学]