Tang Jin-Mei, Li Wen, Xie Yu-Chun, Guo Hong-Wei, Cheng Pei, Chen Huan-Huan, Zheng Xu-Qin, Jiang Lin, Cui Dai, Liu Yun, Ding Guo-Xian, Duan Yu
Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
Exp Toxicol Pathol. 2013 Nov;65(7-8):989-94. doi: 10.1016/j.etp.2013.02.001. Epub 2013 Apr 2.
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the synthesis and secretion of endocrine hormones. To investigate the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on thyroid structure and function, 40 male Wistar rats were divided into 4 equal treatment groups and administered vehicle or one of three doses of PCB118. The experimental groups received intraperitoneal (i.p.) injection of 10, 100, or 1000μg/kg/day PCB118, 5 days per week for 13 weeks, whereas the control group was injected with corn oil (vehicle). Serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) were measured by radioimmunoassays. Histopathological and ultrastructural changes in the thyroid were observed under light microscopy and transmission electron microscopy (TEM). The mRNA expression levels of the sodium-iodide symporter (NIS) and thyroglobulin (TG) were quantified by real-time PCR. Increasing doses of PCB118 resulted in progressively lower FT3, FT4 and TSH concentrations in serum. Injection of PCB118 at all doses led to histopathological deterioration of the thyroid characterized by follicular hyperplasia and expansion, shedding of epithelial cells and fibrinoid necrosis. Follicle cells exhibited swollen or vacuolated endoplasmic reticula, as revealed by TEM. Exposure to PCB118 also caused significant decreases in NIS and TG mRNA expression levels. Chronic exposure to low-dose PCB118 and other PCB congeners may be a significant risk factor for thyroid diseases.
多氯联苯(PCBs)是持久性环境污染物,可严重干扰内分泌激素的合成与分泌。为研究2,3',4,4',5-五氯联苯(PCB118)对甲状腺结构和功能的影响,将40只雄性Wistar大鼠分为4个等量处理组,分别给予赋形剂或三种剂量的PCB118之一。实验组每周5天腹腔注射10、100或1000μg/kg/天的PCB118,共13周,而对照组注射玉米油(赋形剂)。通过放射免疫分析法测定血清中游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)和促甲状腺激素(TSH)的浓度。在光学显微镜和透射电子显微镜(TEM)下观察甲状腺的组织病理学和超微结构变化。通过实时PCR定量钠-碘同向转运体(NIS)和甲状腺球蛋白(TG)的mRNA表达水平。PCB118剂量增加导致血清中FT3、FT4和TSH浓度逐渐降低。所有剂量的PCB118注射均导致甲状腺组织病理学恶化,其特征为滤泡增生和扩张、上皮细胞脱落和纤维蛋白样坏死。透射电子显微镜显示,滤泡细胞的内质网肿胀或空泡化。暴露于PCB118还导致NIS和TG的mRNA表达水平显著降低。长期低剂量暴露于PCB118及其他多氯联苯同系物可能是甲状腺疾病的一个重要危险因素。