Abstract: The aim of the research was to study the effect of individual and combined exposure to lead (Pb）and dinbutyl phthalate(DBP) on the neurological and apoptosis-related gene expressions, and the effect on the nervous system of zebra fish embryos. According to the 3×3 factorial design, 720 zebra fish embryos were randomly divided into 9 groups, Pb (0, 0.01 mg/L,1 mg/L) and DBP (0, 0.005 mg/L,0.5 mg/L) were administered individually and mixtures to zebra fish embryos for 120 h, hatchability and mortality were record. Quantitative real-time PCR was used to assess neurological gene (NR1A, NR2A, NR2D) and apoptosis-related gene (bcl-2, c-fos) expressions. Exposure to individual and combined of Pb and DBP could cause decrease in hatchability and increase in mortality. There was an interaction between Pb and DBP on hatchability and mortality（P＜0.05). Co-exposure to Pb and DBP up-regulated  NR1A, NR2A, NR2D, c-fos gene and down-regulated bcl-2 gene (P<0.05). Exposure to Pb and DBP could impaire the development of zebra fish embryos and cause a certain neurotoxicity. The joint toxicity of them was complicated. It has interaction effect on the hatching rate and mortality and no interaction on neurological gene and apoptosis related genes of zebra fish embryos. The mechanism needs to be further studied.

Key words: lead, dibutyl phthalate, combined exposure, embryo of Danio rerio, gene expression

摘要： 为了研究铅（Pb）和邻苯二甲酸二丁酯（DBP）单独及联合暴露对斑马鱼胚胎神经发育和细胞凋亡相关基因表达的影响，考察 两者对斑马鱼胚胎神经系统的毒性作用。将720个斑马鱼胚胎按3×3析因设计随机分为9组，以Pb（0、0.01 mg/L和1 mg/L）和 DBP(0、0.005 mg/L和0.5 mg/L）单独及联合对斑马鱼胚胎暴露120 h。观察、记录胚胎的孵化、死亡情况，采用荧光定量PCR 测定斑马鱼胚胎神经发育相关基因（NR1A、NR2A、NR2D）和神经细胞凋亡相关基因（bcl-2、c-fos）的表达变化情况。与空白 对照组相比，各暴露组均可致斑马鱼胚胎孵化率降低、死亡率增高(P＜0.05)；联合暴露组NR1A、NR2A、NR2D、c-fos基因表达 水平显著升高， bcl-2基因表达水平显著下降(P＜0.05)。Pb和DBP均可影响斑马鱼胚胎的发育，且具有一定的神经毒性，而二 者联合暴露毒性复杂，对斑马鱼胚胎孵化率和死亡率的影响有交互作用，对神经发育和细胞凋亡相关基因无交互作用，其机制 有待进一步研究。

关键词: 铅, 邻苯二甲酸二丁酯, 联合暴露, 斑马鱼胚胎, 基因表达