SO2长期吸入对大鼠肺组织基因表达谱的影响

采用Affymetrix的基因芯片(RAE230A)技术,研究了SO2长期动态吸入(14mg/m3,1h/d,共30d)后大鼠肺组织基因表达谱的改变.结果表明,与对照组(CK)相比,SO2长期吸入后大鼠肺组织表达上调的基因有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.表明:(1)长期吸入SO2的大鼠肺基因表达谱与其CK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在体内的机理非常复杂;(2)SO2高剂量短期吸入与低剂量长期吸入后,大鼠肺组织基因表达谱的改变很不一致,表明二者在体内的作用机理不同;(3)SO2可引起多种基因的表达发生改变,这意味着多种基因的表达是易变的、不稳定的,在肺组织中可能存在着SO2诱发的表达不稳定型基因组.表1参19

Alteration of Gene Expression Profiles in Rat Lungs Exposed to Sulfur Dioxide for Long Time

Affymetrix GeneChip (RAE230A) analysis was conducted to study the gene expression profiles in the lungs of Wistar rats exposed to SO_ 2 for long time (14 mg/m 3, 1 h/day, for 30 days). It was found that 173 genes, including 79 known genes and 94 novel genes, were up-regulated, and 85 genes, with 46 known and 39 novel ones, were down-regulated in the lungs of rats exposed to SO_ 2 compared with control group. It could be concluded that (1) the discriminating genes in lungs of rats exposed to SO_ 2 for long time included those involved in fatty acid metabolism, immune, inflammatory, oxidative stress, oncogene, tumor suppresser and extracellular matrix. The mechanism of low-dose and long-term exposure to SO_ 2 was very complex; (2) SO_ 2 exerted its effects by different mechanisms in vivo at high-dose and short-term inhalation and at low-dose and long-term inhalation; and (3) expression of many genes in rat lungs was changed by SO_ 2, which implied that the gene expression was changeful and unstable, and there was a genome that its expression might be changed by SO_ 2. Tab 1, Ref 19