三个不同发育关键期PCB153暴露致小鼠发育免疫毒性及其分子机制

项目名称： 三个不同发育关键期PCB153暴露致小鼠发育免疫毒性及其分子机制

项目编号： No.21507048

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 化学工业

项目作者： 赵婷

作者单位： 江苏大学

项目金额： 21万元

中文摘要： PCBs是广泛存在的持久性有毒有机污染物，具有较强的免疫毒性，会导致人类健康损害。PCBs可通过胎盘屏障传递给子代，且发育机体对环境毒物更加敏感，因此，PCBs致发育机体毒性受到广泛关注。基于妊娠期、哺乳期和青春期是三个关键的免疫发育时期，本项目拟采用小鼠母体暴露和幼鼠直接暴露模型，系统研究人体PCBs暴露主要检出物—PCB153致小鼠发育关键期免疫系统的毒性作用，揭示不同发育期小鼠对PCB153毒性的敏感性差异；基于MAPK是PCB153致免疫毒性的主要作用通路，在分子和基因水平探讨PCB153对小鼠发育免疫系统中MAPK-p38，p-p38，JNK，p-JNK，ERK1/2和p- ERK1/2等蛋白表达， EIK-1、ATF-2、CREB等转录因子及即早基因c-fos、c-jun表达的影响，阐明其对小鼠发育免疫毒性的分子机制，为PCBs的健康风险评价提供依据，对人类健康具有重要意义。

中文关键词： 多氯联苯；非共面型PCB153；发育免疫毒性；敏感性；分子机制

英文摘要： PCBs are toxic and persistent organic pollutant, which are commonly found in the natural environment. They are immunotoxic and can cause serious harm to public health on exposure. The toxicity of PCBs can be transmitted to offsprings through placental barrier, and people in the developmental stage are more vulnerable to its attack than those at the maturity stage. Thus, the developmental toxicity induced by PCBs is currently a global concern. Based on the three critical periods of development including gestation, lactation and pubertas, the maternal and pups exposure models were employed to comprehensively investigate the developmental immunotoxicity on mice after exposure to PCB153 in the three critical periods of development. The results may contribute to revealing the sensitivities of organisms in the different developmental stages to the toxicity effect of PCB153. The molecular mechanisms on developmental immunotoxicity would be studied by investigating the expression levels of MAPK-p38，p-p38，JNK，p-JNK，ERK1/2 and p- ERK1/2 proteins, MEF2、EIK-1、ATF-2 and CREB transcription factors, c-fos and c-jun genes, which are based on MAPK is the main signaling pathway for PCB153 induced immunotoxicity effects. The project will provide basis for valuing health risks of PCBs, and possess important significance for public health.

英文关键词： Polychlorinated biphenyl;Non-coplanar type PCB153;Developmental immunotoxicity;Sensibility;Molecular mechanisms