本文選題：鄰苯二甲酸酯　切入點(diǎn)：DEHP　出處：《復(fù)旦大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：鄰苯二甲酸酯(phthalates)主要作為增塑劑使用,添加到塑料中以增強(qiáng)塑料產(chǎn)品的彈性、透明度、耐用性和使用壽命。隨著phthalates的廣泛使用,大量phthalates進(jìn)入生態(tài)環(huán)境,通過食物鏈富集,最終經(jīng)呼吸、飲食、飲水等途徑,進(jìn)入人體,可在尿液、血液、乳汁、脂肪、精液等人體樣品中檢出。近年來,對(duì)phthalates的環(huán)境和人體監(jiān)測數(shù)據(jù)呈指數(shù)性增長,但兒童作為高暴露人群,其體內(nèi)phthalates內(nèi)暴露數(shù)據(jù)亟待補(bǔ)充。 鄰苯二甲酸二乙基己酯(di-2-ethylhexyl phthalate, DEHP)和鄰苯二甲酸二異壬酯(diisononyl phthalate, DINP)是目前使用量最大的兩類phthalates,具有生殖發(fā)育毒性和一定的免疫毒性。己有研究顯示,DEHP暴露對(duì)哮喘發(fā)作呈現(xiàn)免疫佐劑作用,但關(guān)于DINP暴露與哮喘之間的關(guān)聯(lián)研究仍較為缺乏,特別是敏感窗口期暴露的影響。 本研究以探索我國一般人群phthalates暴露全貌為目的,納入、分析了2000年到2012年公開發(fā)表的61篇文獻(xiàn),利用地理信息系統(tǒng)(geographic information system,GIS)分析該類化學(xué)物在環(huán)境介質(zhì)中的濃度及地理分布狀況,利用經(jīng)驗(yàn)公式計(jì)算長江三角洲和珠江三角洲地區(qū)非職業(yè)暴露人群的phthalates攝入量。結(jié)果顯示,過去12年里,我國大部分地區(qū)的phthalates環(huán)境污染逐漸加重,且污染程度存在地區(qū)差異,以廣東省和我國北部地區(qū)污染最為嚴(yán)重；珠江三角洲地區(qū)phthalates和DEHP的人群每日攝入量分別為128.6和61.3μg/kg體重,明顯高于長江三角洲地區(qū)人群(33.9和24.7μg/kg體重)。 在探索我國一般人群暴露水平的基礎(chǔ)上,本研究重點(diǎn)分析了高暴露人群(兒童)DEHP和DINP代謝物的內(nèi)暴露水平。采用高效液相色譜-雙質(zhì)譜聯(lián)用技術(shù)測定了2012年上海市嘉定區(qū)學(xué)齡期兒童393例尿液樣品中DEHP代謝物MEHP、MEHHP、 MEOHP和DINP代謝物MiNP的濃度。結(jié)果顯示,學(xué)齡期兒童普遍檢出MEHP、 MEHHP和MEOHP的暴露,且MEHP、MEHHP、和MEOHP的暴露中位數(shù)分別為1.20、8.79和3.39μg/L:MiNP的檢出水平相對(duì)較低,檢出范圍為未檢出～13.37μg/L,檢出率為21.6%；兒童年齡與其體內(nèi)的phthalates水平呈顯著負(fù)相關(guān)。 鑒于兒童是哮喘的高發(fā)病人群,低年齡兒童是鄰苯二甲酸酯的高暴露人群,且DINP的兒童暴露有上升的趨勢,因此本研究利用動(dòng)物實(shí)驗(yàn)探索DINP生命早期暴露與哮喘的關(guān)聯(lián)及其影響哮喘發(fā)作可能的作用機(jī)制。在宮內(nèi)暴露和哺乳期(孕7天(gestational day (GD)7)至出生后21天(postnatal day (PND)21)), Wistar孕鼠灌胃染毒DINP(染毒濃度分別為5、50和500mg/kg/d,溶劑對(duì)照為玉米油組)；分別于PND22、PND23、PND37對(duì)仔鼠進(jìn)行OVA致敏,PND44天開始對(duì)其進(jìn)行OVA霧化激發(fā),連續(xù)激發(fā)兩天。最后一次霧化激發(fā)后,測定其氣道阻力和肺順應(yīng)性,觀察肺組織病理切片,并測定PI3K/Akt信號(hào)通路相關(guān)細(xì)胞因子的濃度。數(shù)據(jù)顯示,與玉米油對(duì)照組相比,50mg/kg/d DINP染毒組仔鼠的氣道反應(yīng)性增強(qiáng),嗜酸性粒細(xì)胞比例增多,Akt磷酸化程度、NF-κB轉(zhuǎn)錄活性和Th2細(xì)胞因子表達(dá)均增強(qiáng),并與玉米油對(duì)照組間存在統(tǒng)計(jì)學(xué)差異；而5和500mg/kg/d DINP劑量組未發(fā)現(xiàn)明顯免疫促進(jìn)作用。由此可見,一定劑量DINP宮內(nèi)和哺乳期染毒可增強(qiáng)OVA對(duì)F1代仔鼠哮喘發(fā)作的激發(fā)作用,具促敏作用,而PI3K/Akt信號(hào)通路是其促敏作用的可能機(jī)制之一。
[Abstract]:Phthalic acid esters (two phthalates) is mainly used as a plasticizer is added to the plastic plastic products in order to enhance the flexibility, transparency, durability and service life. With the widespread use of phthalates, a large number of phthalates into the ecological environment, enriched through the food chain, eventually by breathing, eating, drinking and other ways to enter the human body, can in the urine, blood, milk, fat, and other human semen samples were detected. In recent years, the phthalates environment and human monitoring data exponentially, but children as high exposure group, the phthalates in vivo exposure data to be added.
The adjacent benzene two formic acid two ethylhexyl (di-2-ethylhexyl phthalate, DEHP) and the adjacent benzene two formic acid two isononylphtalate (diisononyl phthalate DINP) is currently using two kinds of phthalates maximum, with reproductive and developmental toxicity and immune toxicity. It has been showed that DEHP exposure showed immune adjuvant effect on asthma. But the research on association between DINP exposure and asthma are still relatively poor, especially the effects of exposure to sensitive window period.
This study explores phthalates China in the general population exposure picture for the purpose of analysis included 61 papers published in 2000 to 2012, the use of geographic information system (geographic information system, GIS) and the concentration of chemical substances in environment medium physical distribution, non occupation exposure phthalates intake calculation the Yangtze River Delta and Pearl River Delta region using empirical formula. The results show that in the past 12 years, most of China's phthalates environmental pollution is aggravating gradually, the regional difference and the degree of pollution, to Guangdong province and North China's most serious pollution; phthalates and DEHP of the Pearl River Delta region people daily intake respectively. 128.6 and 61.3 g/kg body weight was significantly higher than that of the crowd in the Yangtze River Delta (33.9 and 24.7 g/kg body weight).
In the exploration of the general population in China based on the exposure level, this study focuses on the analysis of the high exposure group (children) DEHP and DINP metabolite exposure level. By high performance liquid chromatography - mass spectrometry for determination of Shanghai city in 2012 for Jiading District school-age children with 393 urine samples of DEHP metabolites of MEHP, MEHHP. The concentration of MEOHP and DINP metabolites of MiNP. The results showed that school-age children generally detected MEHP, MEHHP and MEOHP exposure, and MEHP, MEHHP, and MEOHP respectively. The median exposure detection level 1.20,8.79 and 3.39 g/L:MiNP is relatively low, the detection range is not detected ~ 13.37 g/L, the detection rate was 21.6%; a a significant negative correlation with the age of children in the level of phthalates.
In view of the high incidence of asthma in children is a group of patients, low age children is high population exposed to the adjacent benzene two formic acid ester, and DINP exposed children are on the rise, so this research using animal experiments to explore DINP early life exposure associated with asthma, asthma and its influence mechanism. In utero exposure and lactation (at day 7 (gestational day (GD) 7) to postnatal day 21 (postnatal) day (PND) 21), pregnant Wistar rats by gavage (DINP concentrations were 5,50 and 500mg/kg/d, for corn oil solvent control group); in PND22, PND23, PND37 of rats were sensitized by OVA PND44 day, started to carry on the OVA inhalation, excited for two consecutive days. The last time the atomization excitation, determination of the airway resistance and lung compliance, to observe the pathological section of lung tissue, concentration and determination of PI3K/Akt signaling pathway related cytokines. Data show that with corn oil Compared with the control group, 50mg/kg/d DINP airway reactivity in offspring were increased, the percentage of eosinophil increased phosphorylation of Akt, enhanced expression of NF- kappa B transcription activity and Th2 cytokines, and there were significant differences between the control group and corn oil; and 5 and 500mg/kg/d DINP dose group found no obvious immunological enhancement. Thus, a certain dose of DINP intrauterine and lactation exposure can enhance the effect of OVA on activation of F1 offspring asthma, and sensitive function, and PI3K/Akt signal pathway is one of the possible mechanism of promoting sensitization.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R135

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1 陳麗;我國人群鄰苯二甲酸酯暴露評(píng)估及DINP影響哮喘發(fā)作的機(jī)制研究[D];復(fù)旦大學(xué);2013年

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本文編號(hào)：1632984