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目的研究邻苯二甲酸二(2-乙基)己酯(DEHP)对大鼠甲状腺毒性作用机制及去除暴露因素后的恢复效应。方法 SPF级SD种雄性大鼠按体重随机分为DEHP暴露组及DEHP暴露恢复组,均下设阴性对照亚组(0.0 mg/kg)、低剂量亚组(50.0 mg/kg)、中剂量亚组(158.2 mg/kg)、高剂量亚组(500.0 mg/kg),分别以0.0、50.0、158.2、500.0 mg/kg BW DEHP连续灌胃染毒。DEHP暴露组连续染毒13周,DEHP暴露恢复组经上述染毒后停止染毒并恢复6周。实验结束后处死动物,监测大鼠血清中三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)及促甲状腺素(TSH)的变化情况及甲状腺组织的病理改变;测定大鼠甲状腺组织中谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量。结果 DEHP染毒13周后,大鼠一般情况良好,体重无明显变化。中剂量亚组T4浓度、高剂量亚组T3及T4浓度显著低于阴性对照亚组(均P<0.05)。高剂量亚组甲状腺滤泡体积明显变小,胶质密度下降,滤泡上皮细胞水肿。与阴性对照亚组相比,高剂量亚组甲状腺组织GSH-Px活性降低、MDA含量增加(均P<0.05)。去除暴露因素恢复6周后,DEHP暴露恢复组的甲状腺素水平及甲状腺病理改变与DEHP暴露组比较差异无统计学意义(均P>0.05);大鼠甲状腺组织GSH-Px活性低于DEHP暴露组(P<0.05),MDA含量高于DEHP暴露组(P<0.05)。结论 DEHP对大鼠甲状腺功能有明显损伤作用,其作用机制可能与氧化应激反应有关。去除暴露因素恢复6周后,大鼠甲状腺功能无明显恢复趋势,且DEHP对甲状腺的氧化损伤作用持续加重。因此,DEHP对甲状腺组织有不可逆性的毒性作用。
Objective To study the mechanism of thyroid toxicity induced by di-2-ethylhexyl phthalate (DEHP) and the recovery effect after exposure to exposure factors. Methods SPF male SD rats were randomly divided into DEHP exposure group and DEHP exposure recovery group according to their body weight, and were divided into two groups: negative control group (0.0 mg / kg), low dose group (50.0 mg / kg) Group (158.2 mg / kg) and high dose subgroup (500.0 mg / kg). The rats were orally administered with 0.0, 50.0, 158.2, 500.0 mg / kg BW DEHP respectively. DEHP exposed group for 13 consecutive weeks of exposure, DEHP exposed recovery group after the above-mentioned exposure to the virus and stop the recovery for 6 weeks. Animals were sacrificed at the end of the experiment to monitor the change of serum triiodothyronine (T3), tetraethionine (T4) and thyroid-stimulating hormone (TSH) and the pathological changes of thyroid tissue. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content in thyroid tissue. Results After 13 weeks of DEHP exposure, the rats were generally in good condition with no significant changes in body weight. The concentrations of T3 and T4 in the medium dose subgroup T4 and the high dose subgroup T3 and T4 were significantly lower than those in the negative control subgroup (all P <0.05). High-dose subgroup of thyroid follicular volume was significantly smaller, decreased glial density, follicular epithelial cell edema. Compared with the negative control group, GSH-Px activity and MDA content in thyroid tissue of high-dose subgroup were significantly decreased (all P <0.05). There was no significant difference in thyroid hormone level and thyroid pathological changes between DEHP exposed group and DEHP exposed group (P> 0.05). The activity of GSH-Px in thyroid tissue was lower than that of DEHP exposed group (P <0.05), MDA content was higher than DEHP exposure group (P <0.05). Conclusion DEHP can obviously damage thyroid function in rats, and its mechanism may be related to oxidative stress. Thyroid function did not show a significant recovery trend after six weeks of exposure, and the effect of DEHP on the thyroid oxidative damage continued to increase. Therefore, DEHP has an irreversible toxic effect on thyroid tissue.