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邻苯二甲酸酯暴露对产妇11β–羟基类固醇脱氢酶活性的影响
作者:胡小娅 赵岩 陈北涛 梁园 李露茜 谢长明 张蕴晖 林振浪 谢爱兰 陈尚勤

摘要:

目的  研究产妇尿液中邻苯二甲酸酯类(PAEs)物质代谢物的水平与11β–羟基类固醇脱氢酶(11β–HSD2酶)活性的关联,初步探索PAEs影响胎儿宫内发育的可能机制。方法  2012年采用单纯随机抽样法抽取宫内发育迟缓(IUGR)新生儿33例,并匹配正常对照新生儿33名,采用高效液相色谱–串联质谱法测定产妇尿液中4种PAEs代谢物,即邻苯二甲酸单丁酯(MBP)、邻苯二甲酸(2–乙基己基)单酯(MEHP)、邻苯二甲酸(2–乙基–5羟基己基)单酯(MEHHP)、邻苯二甲酸(2–乙基–5氧己基)单酯(MEOHP)和3种皮质醇皮质酮代谢物,即四氢皮质醇(THF)、allo–四氢皮质醇(allo–THF)、四氢皮质酮(THE)的含量,并分析产妇尿液中PAEs代谢物的水平与11β–HSD2酶活性的关联。结果  66名产妇尿液样本中MBP、MEHP、MEHHP、MEOHP代谢物的检出率分别为98%(65名)、89%(59名)、91%(60名)、91%(60名);病例组母亲尿液样本中MBP、MEHHP、MEOHP和DEHP合计(SumDEHP)的中位数分别为31.20、24.61、11.72和48.67 ng/ml,高于对照组(分别为17.32、12.03、5.68和28.64 ng/ml),差异均具有统计学意义(P值均<0.05);病例组母亲体内11β–HSD2的活性[(THF+allo–THF)/THE=(0.79±0.09) ng/ml]低于对照组[(THF+allo–THF)/THE=(0.58±0.04) ng/ml];男婴母亲尿液中MBP(β′=1.12)、MEHHP(β′=1.14)、MEOHP(β′=1.10)、SumDEHP(β′=1.08)的含量与11β–HSD2的活性呈负相关,差异有统计学意义(P值均<0.05)。结论  PAEs可能通过抑制11β–HSD2的活性影响胎儿宫内发育。

关键词:胎儿生长迟缓;四氢皮质醇;邻苯二甲酸酯;宫内发育迟缓;11β–羟基类固醇脱氢酶

Abstract:

Objective  To study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development.Methods  All of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11β-HSD2 enzyme activity.Results  MBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases), 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11β-HSD2 activity in case group ((THF+allo-THF) /THE= (0.79±0.09) ng/ml) was significantly lower than that of the control group ((THF+allo-THF) /THE= (0.58±0.04) ng/ml); PAEs metabolites MBP (β′=1.12), MEHHP (β′=1.14), MEOHP (β′=1.10), SumDEHP (β′=1.08) in baby boy mother′s urine was reversely correlated to 11β-HSD2 activity.Conclusions  PAEs could affect fetal development by inhibit 11β-HSD2 activity.

Key words: Fetal growth retardation;Tetrahydrocortisol;Phthalate esters;Intrauterine retarded;11β-hydroxy steroid dehydrogenase

发表日期:2014/9

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2014.09.011.T001:表1 产妇尿液几种PAEs代谢物的检出率及含量

    10.3760/cma.j.issn.0253-9624.2014.09.011.T001:表1 产妇尿液几种PAEs代谢物的检出率及含量

  • 10.3760/cma.j.issn.0253-9624.2014.09.011.T002:表2 产妇尿液中THF、THE的含量及(THF+allo–THF)/THE的比值

    10.3760/cma.j.issn.0253-9624.2014.09.011.T002:表2 产妇尿液中THF、THE的含量及(THF+allo–THF)/THE的比值

  • 10.3760/cma.j.issn.0253-9624.2014.09.011.T003:表3 不同性别婴儿母亲的尿液中PAEs的含量与(THF+allo–THF)/THE比值的关联

    10.3760/cma.j.issn.0253-9624.2014.09.011.T003:表3 不同性别婴儿母亲的尿液中PAEs的含量与(THF+allo–THF)/THE比值的关联

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