出生队列儿童1岁龄多环芳烃暴露对其神经发育的影响

发布时间：2018-03-28 19:07

本文选题：多环芳烃　切入点：代谢解毒酶　出处：《青岛大学》2017年硕士论文

【摘要】：目的:通过出生队列研究,探讨队列幼儿出生后12月龄左右多环芳烃(PAHs)暴露对其神经发育的影响。方法:利用问卷调查的形式收集流行病学资料,利用Gesell量表测量幼儿12月龄神经发育,采用LC-MS/MS法测定12月龄幼儿首次晨尿中PAHs的羟基代谢产物(OH-PAH)1-羟基萘、2-羟基萘、2-羟基芴、1-羟基菲、2-羟基菲、3-羟基菲、4-羟基菲、9-羟基菲、1-羟基芘和6-羟基屈等共10种生物标志物的含量;采用Oxi Select?BPDE DNA Adduct ELISA试剂盒测定幼儿脐带血中PAH-DNA加合物;PAHs的关键代谢和解毒酶类基因中谷胱甘肽-S-转移酶M1-02(GSTM1-02)采用多重扩增技术测定其基因分型,其他的单核苷酸多态性(SNP)基因分型采用Sequenom Mass Array系统测定。结果:适应性行为、大运动行为、精细动作行为、语言行为和个人社交行为5大功能区得分均数在96~104之间,各功能区DQ90的幼儿在2.0%~9.8%。10种OH-PAH的检出率在48%~97%,PAH-DNA加合物的检出率为52.4%。Spearman相关分析显示,2-羟基萘、2-羟基芴均与个人社交行为得分负相关(r:-0.132、-0.130);PAH-DNA加合物浓度与适应性行为、大运动行为、精细动作、个人社交行为负相关(r:分别为-0.164、-0.166、-0.171、-0.181)。CYP1A1中rs1048943、rs2606345,CYP1A2的rs762551及GSTM3的rs7483均表现出了与部分功能区的相关性。多元线性回归分析显示,幼儿12月龄OH-PAH浓度均未进入到最后的统计学模型,但是PAH-DNA加合物显示了与神经发育除语言行为能区外的其他能区的相关性,β及其95%CI分别为-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也表现出了与大运动行为的相关性,P=0.028。结论:除了验证了出生前孕期PAHs暴露的健康效应外,幼儿的PAHs代谢和解毒的关键酶类基因多态性值得重视。出生后12月龄PAHs暴露对幼儿12月龄的神经发育影响不能排除,尚需要进一步增加样本量及前瞻性跟踪观察合适的效应检出时间点。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R174

【参考文献】