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DEHP及其代谢产物MEHP对MLTC-1细胞凋亡和类固醇激素合成基因表达的影响 [中文引用][英文引用]

Effects of DEHP and its Metabolite MEHP on Cell Apoptosis and the Expression of Steroidogenic Genes in MLTC-1 Cells

作者:叶婷1  董四君2  王佳3  杨丹1  杨大星1  李灿1 
作者(英文):YE Ting1  DONG Sijun2  WANG Jia3  YANG Dan1  YANG Daxing1  LI Can1 
单位(英文): 
分类号:X171.5
出版年·卷·期(页码):2018·8·第4期(281-287,293)
DOI:
-----摘要:-------------------------------------------------------------------------------------------

目的 实验测评DEHP及其主要代谢产物MEHP暴露对MLTC-1细胞类固醇激素合成关键基因表达的影响。方法 MLTC-1分别暴露于DEHP01101001 000 μmol/L)和MEHP01101001 000 μmol/L24 h,采用Annexin V/PI双染法测定细胞凋亡,并应用荧光定量PCR法分析细胞类固醇激素合成过程中涉及关键酶的基因表达水平。结果 凋亡实验结果显示DEHP1001 000 μmol/L)和MEHP101 000 μmol/L)显著诱导MLTC-1细胞晚期凋亡的发生,1 000 μmol/L DEHPMEHP显著降低了MLTC-1活力。所以本研究采用了较低的染毒浓度(110100 μmol/L)对MLTC-1染毒24 h来评估DEHPMEHPMLTC-1类固醇合成通路的影响。荧光定量结果显示1 μmol/L DEHP显著增加MLTC-1 CYP17A1基因表达水平,而100 μmol/L DEHP显著抑制MLTC-1 CYP17A1CYP11A1SF-1基因表达水平。10 μmol/L DEHP显著增加MLTC-1CYP1A1基因表达水平。100 μmol/L DEHP显著抑制MLTC-1黄体激素受体LHR基因表达水平。1 μmol/L MEHP显著增加MLTC-1 3β-HSD基因表达水平。然而MEHP对类固醇激素合成过程中一些酶如STARCYP17A1CYP11A1、重要调节因子胰岛素样激素3 INSL-3SF-1、关键受体ARLHR基因表达水平均无显著影响。结论 DEHPMEHP诱导MLTC-1凋亡,DEHPMEHP都可影响MLTC-1细胞类固醇激素合成过程中关键基因的表达,从而引起内分泌干扰。

-----英文摘要:---------------------------------------------------------------------------------------

Objectives To study the effects of DEHP and its main metabolite mono (2-ethylhexyl) phthalate (MEHP) exposure on steroidogenesis in MLTC-1. Methods MLTC-1 were exposed to DEHP (0, 1, 10, 100, 1 000 μmol/L) and MEHP (0, 1, 10, 100, 1 000 μmol/L) for 24 h respectively. Apoptosis was detected by Annexin V/PI double staining, and real time quantitative RT-PCR method was conducted to explore the mRNA expression levels of the key enzymes involved in the synthesis of steroid hormones. Results Apoptosis result showed 100 and 1 000 μmol/L DEHP and MEHP significantly induced the late apoptosis of MLTC-1, 1 000 μmol/L DEHP and MEHP significantly reduced the cell viability. Therefore, the lower concentrations of DEHP and MEHP were selected to evaluate the effect of DEHP and MEHP on the steroid synthesis pathway of MLTC-1 in the present study. RT-PCR result showed 1 μmol/L DEHP significantly increased the mRNA expression level of CYP17A1, while 100 μmol/L DEHP significantly inhibited mRNA expression level of CYP17A1, CYP11A1, key regulatory factor (SF-1). 10 μmol/L DEHP significantly increased the expression level of CYP1A1. 100 μmol/L DEHP significantly inhibited the expression of LHR. 1 μmol/L MEHP significantly increased the expression of 3β-HSD. However, MEHP had no significant effect on the expression of some enzymes such as STAR, CYP17A1, CYP11A1, insulin-like hormone 3 (INSL-3), SF-1, AR and LHR. Conclusions DEHP and MEHP promoted MLTC-1 apoptosis and affected the expression of key genes in steroid hormone synthesis of MLTC-1, which may cause endocrine disruption.

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中文著录格式: 叶婷1,,董四君2,,王佳3,,杨丹1,,杨大星1,,李灿1.DEHP及其代谢产物MEHP对MLTC-1细胞凋亡和类固醇激素合成基因表达的影响.环境卫生学杂志.2018;8(4):281-287,293.
英文著录格式: YE,Ting1,,DONG,Sijun2,,WANG,Jia3,,YANG,Dan1,,YANG,Daxing1,,LI,Can1.Effects of DEHP and its Metabolite MEHP on Cell Apoptosis and the Expression of Steroidogenic Genes in MLTC-1 Cells..2018;8(4):281-287,293.

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