本文選題：鄰苯二甲酸酯代謝產(chǎn)物　切入點(diǎn)：臍帶血　出處：《天津醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：研究目的 鄰苯二甲酸酯類化合物主要用作增塑劑,增大產(chǎn)品的可塑性和提高產(chǎn)品的強(qiáng)度,用途廣泛且使用量大,是一類已知的環(huán)境內(nèi)分泌干擾物,可以影響人類和動(dòng)物的正常內(nèi)分泌活動(dòng),從而對(duì)生殖發(fā)育系統(tǒng)造成潛在不良影響。近年來,隨著工業(yè)的發(fā)展,人類對(duì)PAEs的用量不斷增加,PAEs通過各種途徑不斷釋放進(jìn)入環(huán)境,已經(jīng)成為全球范圍內(nèi)最普遍的污染物之一。人體可通過多種途徑攝入PAEs,大量流行病學(xué)調(diào)查顯示人類普遍暴露于PAEs。本研究在優(yōu)化臍帶血清中PAEs代謝產(chǎn)物檢測(cè)方法的基礎(chǔ)上,通過測(cè)定臍帶血清中五種PAEs代謝產(chǎn)物,評(píng)價(jià)胎兒出生前經(jīng)母體PAEs的暴露水平。結(jié)合問卷調(diào)查內(nèi)容,初步探討影響胎兒經(jīng)母體PAEs暴露水平的主要因素,為及時(shí)采取措施預(yù)防出生前經(jīng)母體PAEs暴露產(chǎn)生的危害提供科學(xué)依據(jù)。 研究方法 該研究選取天津地區(qū)96名自愿參加本研究的待產(chǎn)孕婦,排除職業(yè)暴露史和疾病史。收集每名孕婦分娩時(shí)的臍帶血,采用固相萃取高效液相色譜串聯(lián)質(zhì)譜法測(cè)定臍血清中的五種鄰苯二甲酸酯DMP、DEP、DBP、BBP、DEHP各自的代謝產(chǎn)物MMP、MEP、MBP、MBzP、MEHP。 所有調(diào)查對(duì)象均接受流行病學(xué)問卷調(diào)查,主要調(diào)查內(nèi)容包括：一般人口統(tǒng)計(jì)學(xué)特征、職業(yè)暴露史、社會(huì)經(jīng)濟(jì)狀況等,婚育史及疾病史,個(gè)人嗜好(吸煙、飲酒情況)。結(jié)合問卷內(nèi)容及臍帶血中PAEs代謝產(chǎn)物的測(cè)定結(jié)果,采用Logistic回歸分析,初步探討影響胎兒經(jīng)母體PAEs暴露水平的主要因素。 研究結(jié)果 (1)本研究優(yōu)化了同時(shí)測(cè)定臍帶血清中五種PAEs代謝產(chǎn)物的方法,該方法采用p-葡萄糖酸酐酶水解臍帶血清中結(jié)合型鄰苯二甲酸酯代謝物,用磷酸及有機(jī)溶劑(乙腈)去除臍帶血清中的蛋白質(zhì),排除了蛋白質(zhì)對(duì)測(cè)定結(jié)果的干擾,酶解后的溶液采用固相萃取法富集凈化,采用HPLC-MS法對(duì)臍帶血清中五種鄰苯二甲酸酯代謝產(chǎn)物進(jìn)行測(cè)定,該方法回歸方程的回歸系數(shù)均0.99,平均回收率在80.59%～85.75%之間,RSD在3.09%-3.91%之間,檢出限為0.109μg/L-0.579μg/L。 (2)本研究96例臍血清樣本中MMP、MEP、MBP、MBzP、MEHP的檢出率分別為98.96%、94.79%、79.17%、93.75%、98.96%,檢出量中位數(shù)(P25～P75)分別為26.92μg/L (12.50μg/L～59.13μg/L)29.84μg/L)、16.97μg/L(4.03μg/L～40.43μg/L)、3.23μg/L(0.97μg/L-6.76μg/L)、5.48μg/L(3.52μg/L～8.25μg/L)。 (3)經(jīng)過單因素、多因素有序Logistic回歸分析發(fā)現(xiàn),孕期燙染頭發(fā)可能為影響DEP、BBP暴露的危險(xiǎn)因素,OR值分別為3.28(95%CI:1.55-6.95)和4.79(95%CI：2.23～10.3)。孕期使用塑料杯子可能為影響DEHP暴露的危險(xiǎn)因素,OR值為2.66(95%CI.1.21-5.85)。 結(jié)論 本研究建立并優(yōu)化了同時(shí)測(cè)定臍帶血清中五種PAEs代謝產(chǎn)物的固相萃取高效液相色譜-串聯(lián)質(zhì)譜法,該方法回收率較高,重現(xiàn)性較好,適用于臍帶血清中五種鄰苯二甲酸單酯的同時(shí)測(cè)定。應(yīng)用該方法測(cè)定96例胎兒臍血清中五種PAEs代謝產(chǎn)物的含量,測(cè)定結(jié)果表明,胎兒可經(jīng)母體暴露于多種PAES。分析影響孕期PAEs暴露的因素,發(fā)現(xiàn)孕期燙染頭發(fā)可能為影響DEP、BBP暴露的危險(xiǎn)因素,孕期使用塑料杯子可能為影響DEHP暴露的危險(xiǎn)因素。
[Abstract]:research objective
Two phthalate acid esters mainly used as plasticizers, plastic products increase and improve product strength, wide purpose and usage, is a kind of environmental endocrine disruptors known, normal endocrine activity can affect human and animal, and the reproductive system caused by potential adverse effects. In recent years, along with the industry the development of human beings, the amount of PAEs increasing, PAEs through a variety of ways to continue to release into the environment, has become one of the most common pollutants in the world. The human body through a variety of ways a large number of epidemiological studies show that the uptake of PAEs in PAEs. based on the research of optimization method for detection of PAEs metabolites in the serum of umbilical cord generally exposed to human, through the determination of five metabolites of PAEs in umbilical cord serum, evaluation of the fetus before birth by exposure to maternal PAEs. Combined with the content of questionnaire, preliminary exploration The main factors that affect the maternal PAEs exposure level provide a scientific basis for timely measures to prevent the risk of maternal PAEs exposure.
research method
This study selected 96 in Tianjin participated in this study of pregnant women, excluding occupation exposure history and history of disease. Collect childbirth every pregnant woman when the umbilical cord blood by solid phase extraction and high performance liquid chromatography tandem mass spectrometry method for the determination of cord blood serum in five adjacent benzene two formic acid ester DMP, DEP, DBP, BBP, DEHP the metabolites of MMP, MEP, MBP, MBzP, MEHP.
All subjects received questionnaire survey, the main research contents include: general demographic characteristics, occupation exposure, social economic status, marital history and disease history, personal habits (smoking, drinking). The determination results of PAEs metabolites questionnaire and umbilical cord blood, using Logistic regression analysis, the main factors preliminary study on the effect of the fetal maternal PAEs exposure level.
Research results
(1) the optimization method for the simultaneous determination of five metabolites of PAEs in umbilical cord serum, the method using p- glucose anhydride hydrolysis cord serum combined phthalate two carbamate metabolites with phosphoric acid and organic solvent (acetonitrile) removal of the umbilical cord serum protein, protein eliminated the interference on the determination results. Solution after enzymatic hydrolysis by solid phase extraction and enrichment purification of umbilical cord serum concentrations of five kinds of phthalate acid esters of two metabolites were measured by HPLC-MS method, the method of regression coefficient of regression equation is 0.99, the average recovery rate was 80.59% ~ 85.75%, RSD between 3.09%-3.91%, the detection limit is 0.109 g/L-0.579 g/L.
(2) in this study, 96 cases of umbilical cord blood serum samples of MMP, MEP, MBP, MBzP, MEHP detection rates were 98.96%, 94.79%, 79.17%, 93.75%, 98.96%, median detectable amount (P25 ~ P75) were 26.92 g/L (12.50 g/L ~ 59.13 g/L) 29.84 g/L), 16.97 g/L (4.03 g/L ~ 40.43 g/L), 3.23 g/L (0.97 g/L-6.76 g/L), 5.48 g/L (3.52 g/L ~ 8.25 g/L).
(3) after single factor, multi factor ordered Logistic regression analysis found that pregnancy hot hair dyes may affect DEP, risk factors of BBP exposure, the OR values were 3.28 (95%CI:1.55-6.95) and 4.79 (95%CI:2.23 ~ 10.3). The use of plastic cups during pregnancy may affect the risk of DEHP exposure factors, the OR value is 2.66 (95%CI.1.21-5.85).
conclusion
In this study, we established and optimized the simultaneous determination of five kinds of umbilical cord serum metabolites of PAEs in solid phase extraction and high performance liquid chromatography tandem mass spectrometry method, the high recovery rate, good repeatability, suitable for determination of five phthalic acid ester two cord serum at the same time. The content was measured in 96 patients with five fetal umbilical blood. Metabolites of PAEs in the application of this method, the results show that the fetus after maternal exposure to a variety of PAES. analysis on the influencing factors of prenatal PAEs exposure during pregnancy, that hot hair dyes may affect DEP, risk factors of BBP exposure during pregnancy, the use of plastic cup may affect the risk of DEHP exposure factors.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R114

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