目的探讨二氧化硫(SO2)对肝、肺微粒体细胞色素P450两种亚型CYP2B1和CYP2E1 mRNA表达及活性的影响。方法采用SO2动式染毒技术使雄性Wistar大鼠染毒7天,每天6h,SO2的染毒剂量分别为14、28和56mg/m^3。采用分光光度法测定大鼠肝、肺微粒体CYP2E1活性,采用荧光分光光度法测定肝、肺微粒体CYP2B1活性,采用RT-PCR方法测定各组大鼠肝、肺组织中CYP2B1和CYP2E1 mRNA表达水平。结果在肝中,较高剂量的SO2(28和56mg/m^3)可使CYP2B1活性及mRNA水平降低,肝微粒体CYP2E1活性及mRNA在各剂量组均未发生显著改变。肺组织中CYP2B1活性在56mg/m^3剂量组显著降低,但其mRNA水平在28及56mg/m^3剂量组均显著降低;肺微粒体CYP2E1活性及mRNA水平在28及56mg/m^3 SO2处理组均降低显著。结论SO2可降低大鼠肝中CYP2B1和2E1及肺中CYP2B1和CYP2E1的活性及mRNA水平。
Objective To study the effects of sulfur dioxide (SO2) on activities and mRNA expression of hepatic and pulmonary cytochrome P4502B1 and 2E1 in rats. Methods Male Wistar rats were housed in exposure chambers and treated with 14, 28 and 56mg/m^3 SO2 for 6 h/d for 7 days, while control rats were exposed to filtered air in the same condition. The activities of CYP2E1 of rats were measured by spectrophotometry. Fluorescence spectrophotometry was used to study the activities of CYP2B1. The mRNAs of CYP2B1 and 2E1 were analyzed in livers and lungs by using a reverse transcfiption-polymerase chain reaction (RT-PCR) assay. Results In the liver, decreases of CYP2B1 activity and mRNA were observed at higher dose of SO2 (28 and 56mg/m^3 ) . However, the CYP2E1-dependent p-nitrophenol hydroxylases (p- NP) and mRNA were unaltered by SO2 at all detected concentrations. For lungs, CYP2B1 activity was unaltered by SO2 at low concentrations, except for a significant decrease in the rats exposed to SO2 at 56mg/m^3 , however, SO2 at higher concentrations (28 and 56mg/m^3) significantly decreased CYP2B1 mRNA. Significant inhibition of p-NP was observed in lungs of rats exposed to SO2 at 28 and 56mg/m^3 . SO2 at higher concentrations (28 and 56mg/m^3 ) decreased significantly pulmonary CYP2E1 mRNA relative to control animals. Conclusion h was suggested that SO2 exposure could suppress the activites and mRNA expression of hepatic CYP2B1 and pulmonary CYP2B1 and 2E1 of rats.