【作者】 姚永革；

【导师】 詹平；

【作者基本信息】 重庆医科大学 ， 流行病与卫生统计学， 2004， 硕士

【摘要】 目的：利用基因芯片技术探讨壬基酚(nonylphenol，NP)对大鼠F1子代脑早期发育整体基因表达水平的影响，为深入研究环境内分泌干扰物对机体的影响提供科学依据。 方法：SD孕鼠妊娠第7天开始染毒(0，200mg／kg)NP持续到产后第2天，取F1子代2日龄雄性大鼠的脑组织，提取mRNA，采用上海博星基因芯片公司所生产的BiostarR-40S DNA芯片，即4000位点基因芯片，样本经探针标记(对照组cy3，试验组cy5)后与DNA芯片杂交，荧光扫描分析，筛选cy5／cy3比值大于2.0或小于0.5的差异表达基因。 结果：①物质能量代谢相关基因表达：硬脂酰辅酶A脱氢酶(stearyl-CoA desaturase，SCD)、糖原磷酸化酶(glycogen phosphorylase，GPase)、过氧化酶体-2,4-二烯酰-CoA还原酶(peroxisomal 2,4-dienoyl CoA reductase，px-2,4-DCR)、琥珀酸脱氢酶复合体A亚基(succinate dehydrogenase complex，subunit A，SDHA)、促性腺激素调控的长链脂酰辅酶A合成酶(gonadotropin-regulated long chain acyl-CoA synthetase)基因下调。②细胞结构和信息传递相关基因表达：紧密连接蛋白-2(zonula occludens 2 protein，ZO-2)、Ensa(endosulfine 重庆医科大学硕十学位论文 alpha)、ERM一结合磷蛋白(ERM一binding phosphoprotein)、谷氨酸 盐受体(glutamate receptor，ionotropic，AM队2)、内在膜相关蛋白 一(integral membrane一associated proteinl，Itmapl)、I型转谷氨酞 胺酶(transglutaminasel，K polypeptide，Tgml)基因下调。③细胞 色素P45O超家族:CYP3A3基因表达下调，CYP4BI、CYPZC23 基因表达上调。④分类不明确的基因:ESE抗原(ESE antigen)基因 表达下调、sarcosin蛋白(sarcomeric muscle protein)基因表达上调。结论:对已知功能的差异表达基因逐个分析，发现NP可通过多种途径对 机体产生多方面的影响。主要影响神经系统的功能和发育，干扰 内分泌系统功能，影响类固醇激素的合成、代谢，干扰雄性的生 殖功能。更多还原

【Abstract】 Objective: To explore the effects of nonylphenol(NP) on the full gene expression profiles of F1 generation rats by meams of microarry technicue,and to provide scientific basis for further study on effects of environmental endocrine disrupting chemicals on bodiesMethods: Nonylphenol was given to pregnant SD rats from 7days after pregnancy to 2 days post partum at dose of 200mg/kg. Then,gene expression of brain tissue of Fl generation neonatal male rats was determined by using gene chip,probe mark(cy3 and cy5 represented the control the experiment),hybridization and fluorescent scanning to screen out the different expression genes with the ratio of cy5 to cy3 being more than 2.0 or lower than 0.5.Results: (1)Differentially expressed genes associated with substance andenergy metabolism: stearyl-CoA desaturase ( SCD ) , glycogenphosphorylase ( Gpase ) , peroxisomal 2,4-dienoyl CoA reductase( px-2,4-DCR ) , succinate dehydrogenase complex, subunitA(SDHA),gonadotropin-regulated long chain acyl-CoA synthetase genes down-regulated. (2)Differentially expressed genes associated with cell structure and communication: zonula occludens 2 protein(ZO-2), endosulfine alpha, ERM-binding phosphoprotein, glutamate receptor (AMPA2) , integral membrane-associated protein 1 (Itmap1), transglutaminase 1 (Tgm1 ) genes down-regulated. (3) cytochrome P450 superfamily: CYP3A3 gene down-regulated, CYP4B1 CYP2C23 up-regulated. ㏒ome unsorted genes: E5E antigen gene down-regulated, sarcomeric muscle protein gene up-regulated.Conclusion: Extensive effects of NP on bodies in many ways were found by analyzing the differentially expressed genes with defined fuction.lt mainly impacted the function and development of nerve system, disturbed the function of endocrine system,impeded the synthesis and metabolism of steroid hormone and therefore disturbed the reproductive function of the male rats.更多还原