纳米二氧化钛暴露人胚肺细胞差异表达基因相关通路  

Effects of Nano-TiO_2 on Gene Pathway Related Differential Expression Gene in Human Lung

作　　者：孟金萍[1] 孙淑华[1] 王艳蓉[1] 杨旭[1] 吕凤柱[2] 刘云波[1] 张以河[2] 

机构地区：[1]中国医学科学院、北京协和医学院实验动物研究所,北京100021 [2]中国地质大学,北京100083

出　　处：《生态毒理学报》2009年第4期482-487,共6页Asian Journal of Ecotoxicology

基　　金：中央级公益性科研院所基本科研业务费专项资金项目

摘　　要：为探讨纳米二氧化钛(Nano-TiO2)对人胚肺(HPF)细胞差异表达基因相关通路的影响,采用半致死浓度(0.437mg·mL-1)的10nmTiO2暴露体外培养的人胚肺细胞24h,提取RNA,应用基因芯片技术筛选差异表达基因,分析纳米TiO2对基因通路的影响.结果表明,纳米TiO2暴露人胚肺细胞,导致514条肺中表达的基因发生差异表达,涉及多个KEGG通路和BioCarta通路.纳米TiO2暴露人胚肺细胞可能产生以下生物学效应:1)众多位于细胞外区域和细胞膜上的基因(特别是细胞膜受体基因)差异表达,对外界环境胁迫产生应激反应;2)与炎症相关的细胞因子基因表达大量改变,调控细胞的炎症反应;3)钙离子通路的膜受体基因差异表达,导致大量钙离子内流,调控钙离子信号传导;4)某些基因的差异表达(如OCLN下调),降低了细胞紧密联接力;5)与造血细胞增殖和分化相关的基因差异表达,刺激产生大量白细胞以抵抗感染.To investigate the effects of Nano -TiO2 on gene pathway related differential expression gene in human pulmonary fibroblast （HPF） cell, HPF cells were exposed to 10nm Nano -TiO2 particles （0.437mg·mL -1, TCD50 concentration） for 24h. Microarray technique was used to screen out differentiation expressed genes to analyze the influence of Nano -TiO2 on gene pathways. Results show that 514 differentiation expressed genes in lung tissues are found when exposed to Nano -TiO2, which refer to several KEGG pathways and BioCarta pathways. By analyzing these pathways, we conclude that there are some biological effects when HPF cells are exposed to Nano -TiO2 particles, including： 1） Some genes （especially cell membrane receptor） located in extracellular regions and membrane express differentially for the response to external stress; 2） The genes associated with the inflammatory cytokine express differentially, regulating the inflammatory response; 3） Membrane calcium ion channel receptor gene express differentially, resulting in a large amount of calcium influx and regulating calcium signal transduction; 4） Some genes express differentially （such as OCLN downregulation）, resulting in the decrease of cell closely link; 5） The genes associated with the proliferation and differentiation of hematopoietic cells express differentially, stimulating generation of interleukin to resist the infection.

关 键 词：纳米二氧化钛 基因芯片 人胚肺细胞 通路分析 

分 类 号：R994.6[医药卫生—毒理学]