Bai Juli, Meng Ziqiang
Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China.
Regul Toxicol Pharmacol. 2005 Dec;43(3):272-9. doi: 10.1016/j.yrtph.2005.09.002. Epub 2005 Oct 26.
Sulfur dioxide (SO2) is an air pollutant in densely populated areas as well as in areas polluted by coal-fired power plants, smelters, and sulfuric acid factories. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00+/-1.01, 28.00+/-1.77, and 56.00+/-3.44 mg/m3 SO2 for 6 h/day for 7 days, while control rats were exposed to filtered air in the same condition. The mRNA and protein levels of three apoptosis-related genes (p53 and bax are promoters of apoptosis, whereas bcl-2 is apoptotic suppressor) were analyzed in lungs using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and immunohistochemistry method, and caspase-3 activities were detected. The results showed that mRNA levels of p53 and bax were increased in a dose-dependent manner and at the concentrations of 28.00 and 56.00 mg/m3 SO2 the increases were significant (for p53: 1.23-fold at 28 mg/m3 and 1.39-fold at 56 mg/m3; for bax: 1.77-fold at 28 mg/m3 and 2.26-fold at 56 mg/m3, respectively), while mRNA levels of bcl-2 were decreased significantly (0.78-fold at 28 mg/m3 and 0.73-fold at 56 mg/m3) in lungs of rats exposed to SO2. Dose-dependent increase of p53 and bax proteins in the lungs was observed after SO2 inhalation, while decrease of bcl-2 protein levels was obtained using immunohistochemistry method. Caspase-3 activities were increased in lungs of rats after SO2 inhalation. These results lead to a conclusion that SO2 exposure can change the expression of apoptosis-related genes, and it suggests that SO2 can induce apoptosis in lung of rat and may have relations with some apoptosis-related diseases. Elucidating the expression patterns of those factors after SO2 inhalation may be critical to our understanding mechanisms of SO2 toxicity and helpful for the therapeutic intervention.
二氧化硫（SO₂）是人口密集地区以及受燃煤发电厂、冶炼厂和硫酸厂污染地区的一种空气污染物。在本研究中，将雄性Wistar大鼠饲养在暴露舱中，分别用14.00±1.01、28.00±1.77和56.00±3.44 mg/m³的SO₂处理，每天6小时，共7天，而对照大鼠在相同条件下暴露于过滤空气中。使用实时逆转录-聚合酶链反应（实时RT-PCR）分析和免疫组织化学方法分析肺中三个凋亡相关基因（p53和bax是凋亡促进因子，而bcl-2是凋亡抑制因子）的mRNA和蛋白质水平，并检测caspase-3活性。结果表明，p53和bax的mRNA水平呈剂量依赖性增加，在28.00和56.00 mg/m³的SO₂浓度下，增加显著（对于p53：28 mg/m³时为1.23倍，56 mg/m³时为1.39倍；对于bax：28 mg/m³时为1.77倍，56 mg/m³时为2.26倍），而暴露于SO₂的大鼠肺中bcl-2的mRNA水平显著降低（28 mg/m³时为0.78倍，56 mg/m³时为0.73倍）。吸入SO₂后，观察到肺中p53和bax蛋白呈剂量依赖性增加，而使用免疫组织化学方法检测到bcl-2蛋白水平降低。吸入SO₂后，大鼠肺中caspase-3活性增加。这些结果得出结论，SO₂暴露可改变凋亡相关基因的表达，这表明SO₂可诱导大鼠肺细胞凋亡，并且可能与某些凋亡相关疾病有关。阐明吸入SO₂后这些因子的表达模式可能对于我们理解SO₂毒性机制至关重要，并有助于治疗干预。
