六溴环十二烷(HBCD)对H4细胞和SK-N-AS细胞脱碘酶2和3表达的影响Effect of Hexabromocyclododecane( HBCD) on the Expressions of Deiodinases 2 and 3 in the Human Neuroglioma H4 Cells and Neuroblastoma SK-N-AS Cells
郝小吉;尚小娜;于海华;么建萍;韩璐;刘晓晖;李亚晨;邵静;
摘要(Abstract):
六溴环十二烷(hexabromocyclododecane,HBCD)与多溴联苯醚(polybrominated diethyl ethers,PBDEs)复合污染体系,对人类健康尤其神经系统所造成的潜在危害及其机制一直是笔者课题组的研究方向。HBCD是广泛使用的溴化阻燃剂,与PBDEs一样,会通过干扰内分泌系统、影响甲状腺激素分泌及损伤神经系统,对生物体产生发育神经毒性。作为系列研究之一,本研究以H4人脑神经胶质瘤细胞和SK-N-AS人神经母细胞瘤细胞为体外生物模型,通过观察HBCD对H4细胞Ⅱ型脱碘酶(Dio2)和SK-N-AS细胞Ⅲ型脱碘酶(Dio3)表达的调控,初步探讨了HBCD对神经系统局部甲状腺激素水平的潜在影响。H4细胞和SK-N-AS细胞分别暴露于0、1、3和9μmol·L-1HBCD 24 h后,采用MTT法检测细胞活力,Western Blot和RT-PCR法分别分析Dio2和Dio3蛋白和基因的表达,酶联免疫吸附测定(ELISA)法检测H4细胞脑源性神经细胞营养因子(BDNF)的分泌。结果表明,HBCD以剂量依赖方式降低H4细胞和SK-N-AS细胞生存率,引起H4细胞Dio2蛋白和基因表达下调,而致SK-N-AS细胞Dio3蛋白和基因表达上调。此外,HBCD还降低H4细胞BDNF的分泌。这表明,HBCD很可能通过影响神经和胶质细胞脱碘酶的表达,影响脑局部甲状腺激素水平,从而引起神经系统损伤及发育神经毒性。
关键词(KeyWords): 六溴环十二烷;H4细胞;SK-N-AS细胞;神经毒性;脱碘酶
基金项目(Foundation): 国家自然科学基金(81773389,81273031);; 大连医科大学教学改革研究项目(DYLX16053)
作者(Author): 郝小吉;尚小娜;于海华;么建萍;韩璐;刘晓晖;李亚晨;邵静;
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DOI:
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