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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 Ammonium Perchlorate (AP) to the thyroid gland of ovariectomization (OVX) and to obtain the LOAEL and BMDL10 values. Methods Sixty female SD rats were randomly divided into sham operation (SHAM) control group, OVX control group and 4 AP treatment groups (50, 100, 250 and 500 mg / kg · bw) for 8 days. The activities of type 1 5’-deiodinase (5’-DI), serum T3, T4, and thyrotropin TSH) levels were observed thyroid histopathology, thyroid organ coefficient and thyroid epidermis / glial ratio. The minimum NOAEL and LOAEL observed for adverse effects and the lower confidence limit (BMDL) for baseline dose (BMD) were obtained. Results The body weight and weight gain in OVX group were significantly higher than those in SHAM control group (P <0.01). There was no significant difference in body weight between OVX groups (P> 0.05). The changes of serum T4, TSH, thyroid organ coefficient and epidermal / glial ratio in each dose group were statistically significant (P <0.05), but the changes of 5’-DI enzyme activity were not statistically significant (P> 0.05 ). Serum T3 in 250 and 500 mg / kg · bw dose groups was significantly lower than that in OVX control group (P <0.01). There were different degrees of histopathological damage in the thyroid of AP dose groups. LOAEL was 50 mg / kg · bw for AP on serum T3, T4 and TSH levels, thyroid organ coefficient and thyroid epidermis / glial ratio in OVX rats, and BMDL10 was 15 mg / kg · bw. Conclusion AP has a significant dose-response relationship with thyroid interference in OVX rats. LOAEL of AP on thyroid in ovariectomized rats was 50 mg / kg · bw and BMDL10 was 15 mg / kg · bw.