采用Affymetrix的基因芯片(RAE230A)研究了SO2短期(56mg/m^3,6h/day,for 7 days)及长期(14mg/m^3,1h/day,for 30 days)吸入后时大鼠肺基因表达谱改变的影响.结果表明,与其相应的时照组相比,SO2短期吸入后表达上调的基因有31个,其中包括18个已知基因和13个新基因,而表达下调的基因有30个,其中包括19个已知基因和11个新基因;SO2长期吸入后表达上调的基因有173个,其中包括79个已知基因和94个新基因,而表达下调的基因有85个,其中包括46个已知基因和39个新基因.由此结论:1)高剂量短期吸入与低剂量长期吸入SO:在体内的作用机理不同;2)短期吸入SO2的大鼠肺基因表达谱与其时照组相比,氧化磷酸化相关的一些基因发生了变化,这表明高剂量短期吸入SO2可能导致线粒体功能的恶化;3)长期吸入SO2的大鼠肺基因表达谱与其对照组相比,表达有差异的基因涉及到脂肪酸代谢、免疫、炎症、氧化应激、原癌基因、肿瘤抑制基因和细胞外基质等,表明低剂量长期吸入SO2在体内的机理要更为复杂.本研究证明,在基因组中存在一些基因,它们的表达时环境污染物很敏感,可被称为环境表达不稳定基因组.
Affymetrix GeneChip (RAE230A) analysis was carried to analyze the gene expression profiles of the lungs of Wistar rats short-term (20ppm, 6 h/day, for 7 days) and long-term (5 ppm, 1 h/day, for 30 days) exposed to SO2. The results showed that 31 genes, containing 18 known genes and 13 novel genes, were up-regulated ,and 30 genes, containing 19 known genes and 11 novel genes, were down-regulated in rats short-term exposed to SO2 compared with the control rats. While there were 173 genes, containing 79 known genes and 94 novel genes, were up-regulated, and 85 genes, containing 46 known genes and 39 novel genes, were down-regulated in rats long-term exposed to SOz compared with control rats. These results lead to the conclusions: (1)SO2 exerted its effects by different mechanisms in vivo at high-dose shortterm inhalation and at low-dose long-term inhalation; (2) A notable feature of the gene expression profile was the changed expression of genes related to oxidative phosphorylation in lungs of rats short-term ex- posed to SOz, which shows high-dose short-term exposed to SO2 may cause the deterioration of mitochondrial functions; (3)Discriminating genes in lungs of rats long-term exposed to SO2 included those involved in fatty acid metabolism, immune, inflammatory, oxidative stress, oncogene, tumor suppresser and extracellular matrix. The mechanism of low-dose long-term exposed to SO2 is more complex. It was proved that there was an expression unsteady genome to SO2 or environmental pollutants in total genome of rat lung.