DEHP致大鼠甲状腺毒性作用中的机制研究  

Mechanism of the thyroid toxicity in rats exposured to di-2-ethylhexyl phthalate

作　　者：胡帅尔[1] 张紫虹[1] 杨美玲[1] 李文立[1] 黄建康[1] 陆彦[1] 王凤岩[1] 董活波 

机构地区：[1]广东省疾病预防控制中心毒理所,广东广州511430

出　　处：《毒理学杂志》2014年第2期87-90,共4页Journal of Toxicology

基　　金：国家自然科学基金(81302433)

摘　　要：目的探讨自噬在邻苯二甲酸二(2-乙基)己酯(DEHP)致雄性大鼠甲状腺毒性作用中的机制。方法 SD种雄性大鼠24只,随机分为4组,每组6只。用50.0、158.2和500.0 mg/kg·bw DEHP连续灌胃染毒4周,动态观察大鼠的一般情况和体重变化;检测不同浓度DEHP染毒后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病理改变;测定大鼠血清、甲状腺组织中超氧化物歧化酶(SOD)及活性氧(ROS)水平;Western blot检测LC3和p62蛋白表达变化。结果 DEHP染毒后,大鼠体重无明显变化。光学显微镜下可见高剂量组甲状腺滤泡体积变小,腔内胶质密度下降。DEHP高剂量染毒组大鼠血清T3和T4水平显著下降。高剂量组血清及甲状腺组织SOD活性下降,而ROS升高,与对照组比较差异均有统计学意义(P<0.05)。Western blot结果显示DEHP可显著上调甲状腺组织中LC3Ⅱ蛋白表达、下调p62蛋白表达,表明DEHP作用下甲状腺组织自噬活性增加。相关性分析结果显示ROS与LC3Ⅱ蛋白表达成正相关,与p62蛋白表达成负相关。结论 DEHP可通过氧化应激引起甲状腺功能减退,同时可通过诱导自噬,降低ROS对细胞的毒性伤害,提示自噬是DEHP致甲状腺毒性作用中的自我保护机制。Objective To investigate the effect of autophagy in the thyroid toxicity of male rats exposure to di-2-ethylhexyl phthalate. Methods 24 Sprague Dawley male rats were divided into 4 groups randomly, each group including 6 rats. Animals were exposed to 50.0,158.2 and 500. 0 mg/kg, bw DEHP by garage for 4 weeks. The general conditions and body weight were observed. At the end of the exposure, pathological changes of the thyroid tissue and T3 ,T4 ,TSH level were examined, SOD and ROS of blood and thyroid tissue were measured. Then,Western blot was performed to examine the expression of p62 and LC3. Results In the thyroid, a reduction in the size of follicles and decrease in colloid density were seen at 500. 0 mg/kg.bw DEHP. Compared to control, T3 ,T4 level remarkably decreased at 500.0 mg/kg.bw DEHP dosage, SOD in blood and thyroid tissue dramatically decrease, while ROS level increased at 500.0 mg/kg, bw DEHP dosage. For Western bloting, LC3-Ⅱ was dramatically increased at protein level, while p62 was significantly decreased at 158.2 and 500. 0 mg/kg-bw DEHP dosage. Correlation analysis showed that ROS was positively correlated with LC3 Ⅱ protein level, while ROS was negatively correlated with p62 protein expression. Conclusion DEHP has toxicant effects on thyroid in rats by oxidative stress injuries, autophagy was induced to reduce ROS cytotoxicity injury, suggesting that autophagy plays self-protection role in DEHP-induced thyroid toxicity.

关 键 词：自噬 邻苯二甲酸二(2-乙基)己酯 活性氧 甲状腺毒性 

分 类 号：R114[医药卫生—卫生毒理学]