Dechlorane 602的毒性效应及分子机制研究

发布时间：2018-02-03 08:49

本文关键词： Dechlorane 602 类雌激素效应雌激素受体蛋白表达谱　出处：《大连海事大学》2017年硕士论文　论文类型：学位论文

【摘要】：得克隆602(Dechlorane 602,Dec602)是一种氯代阻燃剂,广泛存在于各种环境和生物介质中,与目前广泛使用的阻燃剂得克隆(DechloranePluS,DP)结构类似,二者都具有持久性、生物富集性、生物放大性等特征。与DP相比,Dec602具有更强的生物富集能力,对人类健康和生态环境构成了潜在的威胁。本研究通过体外(in vitro)和体内(invivo)暴露实验,探讨了 Dec602的毒性效应及可能的分子机制。体外研究表明,Dec602具有类雌激素效应,在10~(-10)M～10~(-6)M范围内,能够诱导人乳腺癌MCF-7细胞增殖,且具有时间-和剂量-效应关系。Dec602通过上调细胞周期蛋白CyclinDl的基因表达,推动细胞周期由Gl期向S期转换,加速细胞周期进程,进而促进细胞增殖。基因和蛋白的定量分析表明,Dec602暴露使MCF-7细胞中雌激素受体α(Estrogenreceptor,ERα)mRNA和蛋白表达水平升高,但不能影响芳香烃受体(Aryl hydrocarbon receptor,AhR)的表达和合成,推测Dec602的类雌激素效应主要通过影响ERα表达或由ER介导。体内暴露实验采用雄性C57BL/6小鼠进行Dec602(1μg/kg · bw)连续口服暴露7天,采集肝脏组织进行双向电泳(2D-PAGE)分析。从肝脏蛋白表达谱中共获得15个差异表达的蛋白点,质谱分析表明,这些蛋白主要参与氧化损伤、物质和能量代谢以及信号转导通路。本研究明确了 Dec602具有类雌激素效应,通过ER介导的途径诱导MCF-7细胞增殖。同时,通过对小鼠肝脏蛋白表达谱的分析,揭示了 Dec602暴露会造成小鼠肝脏的氧化损伤,干扰物质代谢、能量代谢以及信号转导通路。这为客观评价Dec602的生物毒性和生态风险提供了科学依据。
[Abstract]:To clone 602 (Dechlorane 602, Dec602) is a kind of chlorinated flame retardant, widely exists in various environmental and biological medium, with the widely used flame retardant Dechlorane (DechloranePluS, DP) two have the similar structure, persistence, bioaccumulation, biomagnification and other characteristics. Compared with DP that Dec602 has stronger ability of biological enrichment, which is a potential threat to human health and ecological environment. This study by in vitro and in vivo (in vitro) (invivo) exposure experiments, discusses the toxic effects of Dec602 and the possible molecular mechanism. The research indicated that the body, Dec602 has estrogenic effect, in the 10~ (-10 M) ~ 10~ (-6) in the range of M, to the proliferation of human breast cancer cells induced by MCF-7, and has.Dec602 time - and dose effect through upregulation of cyclin CyclinDl gene expression, promote cell cycle transition from Gl phase to S phase, accelerate cell cycle During the process, and promote cell proliferation. The gene and protein quantitative analysis showed that Dec602 exposure to estrogen receptor alpha MCF-7 cells (Estrogenreceptor, ER alpha) increased expression of mRNA and protein, but does not affect the aryl hydrocarbon receptor (Aryl hydrocarbon, receptor, AhR) expression and synthesis of estrogenic effect that Dec602 mainly expressed the effect of ER alpha or mediated by ER. In vivo exposure experiments using male C57BL/6 mice of Dec602 (1 g/kg BW) orally exposed for 7 days to collect liver tissue by two-dimensional electrophoresis (2D-PAGE) analysis. The liver protein expression profiles were obtained 15 differentially expressed protein spots, mass spectrometry analysis showed that these proteins are mainly involved in oxidative damage, material and energy metabolism and signal transduction pathways. This study clarified that Dec602 has estrogenic effect, by way of ER mediated MCF-7 induced cell proliferation. At the same time, through After analyzing the protein expression profiles of mice liver, it is revealed that Dec602 exposure can cause oxidative damage in mice liver, interfere with substance metabolism, energy metabolism and signal transduction pathway. This provides a scientific basis for objectively evaluating the biological toxicity and ecological risk of Dec602.

【学位授予单位】：大连海事大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R99

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