新型溴化阻燃剂DBDPE对人甲状腺细胞Nthy-ori3-1的毒性研究  

The toxicity of new brominated flame retardant DBDPE on Nthy-ori3-1 cell line

作　　者：王振余 张海晨 肖倩倩 袁约瑟 葛建鸿 张琼 王晓芸 江宛谕 荘溢濛 崔原 孟庆贺 蒋建军 郝卫东 魏雪涛 WANG Zhen-yu;ZHANG Hai-chen;XIAO Qian-qian;YUAN Yue-se;GE Jian-hong;ZHANG Qiong;WANG Xiao-yun;JIANG Wan-yu;ZHUANG Yi-meng;CUI Yuan;MENG Qing-he;JIANG Jian-jun;HAO Wei-dong;WEI Xue-tao(Department of Toxicology,School of Public Health,Peking University,Beijing 100191,China;Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety,Beijing 100191,China)

机构地区：[1]北京大学医学部公共卫生学院毒理学系,北京100191 [2]食品安全毒理学研究与评价北京市重点实验室,北京100191

出　　处：《毒理学杂志》2023年第5期369-374,382,共7页Journal of Toxicology

摘　　要：目的为了初步探索十溴二苯乙烷[1,2-Bis(2,3,4,5,6-pentabromophenyl)ethane,DBDPE]对人体的不良效应,以人源甲状腺滤泡上皮细胞系Nthy-ori3-1为研究对象,观察其甲状腺毒性及机制,为其风险评估提供科学依据。方法用不同浓度的DBDPE染毒Nthy-ori3-1细胞24 h,通过MTT和CFSE法分别检测细胞活力和细胞增殖能力,通过Western blot检测甲状腺激素合成关键蛋白甲状腺球蛋白(thyroglobulin,TG)、甲状腺过氧化物酶(thyroid peroxidase,TPO)、钠碘共转运体(sodium-iodine cotransporter,NIS)和调控蛋白同源盒蛋白8(paired box gene 8,PAX8)、甲状腺转录因子1(thyroid transcription factor1,TTF1)和甲状腺转录因子2(thyroid transcription factor2,TTF2)表达变化。结果2和20 mg/L DBDPE使细胞活力降低(F=2.59,F=11.43,P<0.05),细胞增殖能力无明显变化。20 mg/L DBDPE使TPO蛋白表达降低(F=2.52,P<0.05),2和20 mg/L DBDPE使NIS蛋白表达降低(F=3.78,F=11.34,P<0.05)。进一步检测了控制关键蛋白合成的调控蛋白PAX8、TTF1和TTF2表达情况,结果显示2 mg/L DBDPE使PAX8蛋白表达降低(F=3.78,P<0.05),2和20 mg/L DBDPE使TTF1蛋白表达降低(F=7.12,F=3.13,P<0.05),20 mg/L DBDPE使TTF2蛋白表达降低(F=4.05,P<0.05)。结论DBDPE能够抑制甲状腺激素合成过程,对人体可能具有甲状腺毒性风险。Objective In order to confirm whether DBDPE has adverse effect on human health,human-derived thyroid follicular epithelial cell line Nthy-ori3-1 was selected to observe the thyroid toxicity and potential mechanism,so as to provide scientific basis for its risk assessment.Methods Nthy-ori3-1 cells were exposed to different concentrations of DBDPE for 24 hours.The changes of cell viability and proliferation were detected by MTT and CFSE method respectively.The expressions of key proteins TG,TPO,NIS and regulatory proteins PAX8,TTF1,TTF2 for the synthesis of thyroid hormone were measured by Western blot.Results DBDPE at 2 and 20 mg/L decreased cell viability,but there was no significant change in cell proliferation(F=2.59,F=11.43,P<0.05).DBDPE at 20 mg/L reduced the expressions of TPO(F=2.52,P<0.05),while 2 and 20 mg/L DBDPE decreased the expressions of NIS(F=3.78,F=11.34,P<0.05).Furthermore,the expressions of PAX8,TTF1 and TTF2,which control the synthesis of key proteins about T4,were detected.The result showed that the expression of PAX8 was lower in the 2 mg/L DBDPE treatment group(F=3.78,P<0.05).Protein levels of TTF1 were decreased after 2 and 20 mg/L DBDPE exposure(F=7.12,F=3.13,P<0.05).DBDPE at 20 mg/L lessened the protein levels of TTF2(F=4.05,P<0.05).Conclusion DBDPE can inhibit the synthesis of thyroid hormone and pose a risk of thyroid toxicity to humans.

关 键 词：十溴二苯乙烷 Nthy-ori3-1细胞 甲状腺激素合成蛋白 调控蛋白 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]