论文部分内容阅读
目的:探讨2,2’,4,4’-四溴联苯醚(BDE-47)对视黄醛受体(RXRα)和雌激素受体(ERα,ERβ)的影响,为阐明多溴联苯醚化合物神经内分泌干扰效应提供科学依据。方法:采用CCK-8法测定BDE-47对慢病毒转染技术构建的稳定高表达和低表达RXRα的MCF-7细胞系及正常细胞系的细胞毒性;并以BDE-47分别处理3种细胞,采用TBA法、XOD法及RT-PCR法测定超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量及人类8-羟基鸟嘌呤DNA糖苷酶(hOGG1)mRNA表达量,采用RT-PCR和Western blot分析其对3种细胞系RXRα、ERα和ERβ的mRNα及蛋白表达的影响。结果:BDE-47对MCF-7细胞系具有明显的细胞毒性作用,作用24 h时,对RXRα正常表达、高表达和低表达的MCF-7细胞的半数抑制浓度(IC_(50)分别为23.15、82.78、30.16μmol/L;BDE-47可造成3种细胞的氧化损伤,RXRα受体高表达细胞对BDE-47的细胞毒性耐受性明显高于另外两种细胞,可一定程度提高细胞抗氧化损伤能力。BDE-47对3种细胞RXRα的表达有明显的抑制作用,可诱导RXRα正常表达与低表达细胞中ERα受体的表达增强、ERβ受体的表达降低;而在RXRα高表达细胞中ERα受体的表达降低、ERβ受体的表达增强,两种雌激素受体表达变化相反。结论:BDE-47可能抑制RXRα受体表达,继而干扰ERα、ERβ两种受体的表达和二者间的平衡,从而发挥其神经内分泌毒性效应。
Objective: To investigate the effects of 2,2 ’, 4,4’-tetrabromodiphenyl ether (BDE-47) on the retinaldehyde receptor (RXRα) and estrogen receptor (ERα, ERβ) Neuroendocrine interference effect to provide a scientific basis. Methods: CCK-8 method was used to determine the cytotoxicity of BDE-47 to MCF-7 cell lines and normal cell lines with stable expression of RXRα and low expression of RXRα. Three kinds of cells were treated with BDE-47 The activities of superoxide dismutase (SOD), malondialdehyde (MDA) and the expression of human 8-oxoguanine DNA glycosylase (hOGG1) mRNA were determined by TBA, XOD and RT-PCR. PCR and Western blot analysis of the three cell lines RXRα, ERα and ERβ mRNα and protein expression. Results: BDE-47 had obvious cytotoxicity on MCF-7 cell line, and the IC50 of MCF-7 cells with normal expression, high expression and low expression of RXRα at 24 h were 23.15 , 82.78,30.16μmol / L; BDE-47 can cause oxidative damage of three kinds of cells, and the cytotoxicity of BDE-47 cells with high expression of RXRα receptor was significantly higher than that of the other two cells, Oxidative damage.BDE-47 significantly inhibited the expression of RXRα in all three kinds of cells, and induced the expression of ERα receptor in normal and low expression cells of RXRα and decreased the expression of ERβ receptor; while in RXRα-overexpressing cells The expression of ERα receptor was decreased, the expression of ERβ receptor was enhanced, and the changes of the two estrogen receptors were opposite.Conclusion: BDE-47 may inhibit the expression of RXRα receptor and then the expression of ERα and ERβ receptors, Between the balance, to play its neuroendocrine toxicity effect.