本文選題：多環(huán)芳烴　切入點：代謝解毒酶　出處：《青島大學》2017年碩士論文

【摘要】：目的:通過出生隊列研究,探討隊列幼兒出生后12月齡左右多環(huán)芳烴(PAHs)暴露對其神經(jīng)發(fā)育的影響。方法:利用問卷調(diào)查的形式收集流行病學資料,利用Gesell量表測量幼兒12月齡神經(jīng)發(fā)育,采用LC-MS/MS法測定12月齡幼兒首次晨尿中PAHs的羥基代謝產(chǎn)物(OH-PAH)1-羥基萘、2-羥基萘、2-羥基芴、1-羥基菲、2-羥基菲、3-羥基菲、4-羥基菲、9-羥基菲、1-羥基芘和6-羥基屈等共10種生物標志物的含量;采用Oxi Select?BPDE DNA Adduct ELISA試劑盒測定幼兒臍帶血中PAH-DNA加合物;PAHs的關鍵代謝和解毒酶類基因中谷胱甘肽-S-轉(zhuǎn)移酶M1-02(GSTM1-02)采用多重擴增技術(shù)測定其基因分型,其他的單核苷酸多態(tài)性(SNP)基因分型采用Sequenom Mass Array系統(tǒng)測定。結(jié)果:適應性行為、大運動行為、精細動作行為、語言行為和個人社交行為5大功能區(qū)得分均數(shù)在96~104之間,各功能區(qū)DQ90的幼兒在2.0%~9.8%。10種OH-PAH的檢出率在48%~97%,PAH-DNA加合物的檢出率為52.4%。Spearman相關分析顯示,2-羥基萘、2-羥基芴均與個人社交行為得分負相關(r:-0.132、-0.130);PAH-DNA加合物濃度與適應性行為、大運動行為、精細動作、個人社交行為負相關(r:分別為-0.164、-0.166、-0.171、-0.181)。CYP1A1中rs1048943、rs2606345,CYP1A2的rs762551及GSTM3的rs7483均表現(xiàn)出了與部分功能區(qū)的相關性。多元線性回歸分析顯示,幼兒12月齡OH-PAH濃度均未進入到最后的統(tǒng)計學模型,但是PAH-DNA加合物顯示了與神經(jīng)發(fā)育除語言行為能區(qū)外的其他能區(qū)的相關性,β及其95%CI分別為-0.314(-0.591,-0.036)、-0.461(-0.801,-0.121)、-0.565(-0.920,-0.210)、-0.540(-0.873,-0.206)。CYP1A2的rs762551也表現(xiàn)出了與大運動行為的相關性,P=0.028。結(jié)論:除了驗證了出生前孕期PAHs暴露的健康效應外,幼兒的PAHs代謝和解毒的關鍵酶類基因多態(tài)性值得重視。出生后12月齡PAHs暴露對幼兒12月齡的神經(jīng)發(fā)育影響不能排除,尚需要進一步增加樣本量及前瞻性跟蹤觀察合適的效應檢出時間點。
[Abstract]:Objective: to investigate the effects of PAHs exposure on the neurodevelopment of children in the cohort by birth cohort study. Methods: epidemiological data were collected by questionnaire. Gesell scale was used to measure the nerve development of children at 12 months of age. Determination of the hydroxyl metabolites of PAHs in the first morning urine of children aged 12 months by LC-MS/MS method: OH-PAHN 1-hydroxy-naphthalene 2-hydroxy-naphthalene 2-hydroxy-phenanthroline 2-hydroxy-phenanthroline 3-hydroxyphenanthroline 3-hydroxyphenanthroline 4-hydroxy-phenanthroline 1-hydroxypyrene and 6-hydroxyl flexion. Content of biomarkers; Adopt Oxi Select? BPDE DNA Adduct ELISA kit was used to determine the key metabolism of PAH-DNA adducts and glutathione -Stransferase M1-02GSTM1-02 in umbilical cord blood of infants. The other single nucleotide polymorphisms (SNPs) genotypes were determined by Sequenom Mass Array system. Results: the mean scores of the five major functional areas, adaptive behavior, large motor behavior, fine motor behavior, language behavior and personal social behavior, ranged from 96 to 104. The detectable rate of PAH-DNA adducts in children with DQ90 in each functional area was 9.80.The detectable rate of PAH-DNA adducts was 48 / 97. The results of 52.4%.Spearman correlation analysis showed that there was a negative correlation between PAH-DNA adducts and individual social behavior scores (r: -0.132 ~ -0.130), and between PAH-DNA adducts concentration and adaptive behavior, large exercise behavior. Rs762551 of rs1048943rs2606345CYP1A2 and rs7483 of GSTM3 showed the correlation with some functional regions. Multivariate linear regression analysis showed that the concentration of OH-PAH in children at 12 months did not enter the final statistical model, the results of multiple linear regression analysis showed that the concentration of OH-PAH in children at 12 months of age did not reach the final statistical model, and the correlation between rs7483 of rs1048943 and CYP1A2 of CYP1A2 was higher than that of CYP1A1, and the correlation between rs7483 of rs1048943 and CYP1A2 was significant. However, the PAH-DNA adduct showed a correlation with other energy regions of neurodevelopment other than language behavioral ability, 尾 and its 95%CI were -0.314- 0.591U -0.0361U -0.461U -0.801U -0.121U -0.565U -0.920U -0.21040-0.873mb -0.206N CYP1A2, respectively. Conclusion: in addition to verifying the relationship between rs762551 and large motor behavior before birth, the rs762551 of CYP1A2 also showed a correlation with large motor behavior. In addition to the health effects of PAHs exposure, The key enzyme gene polymorphisms of PAHs metabolism and detoxification in young children should be paid attention to. The effects of PAHs exposure at 12 months after birth on the neurodevelopment of children at 12 months of age cannot be excluded. It is necessary to further increase the sample size and to observe the appropriate time point of effect detection by prospective tracking.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R174

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