二氧化硫对大鼠细胞色素P4501A的抑制作用

秦国华; 孟紫强

doi:10.11847/zgggws2006-22-09-30

二氧化硫对大鼠细胞色素P4501A的抑制作用

Inhibition of sulfur dioxide on cytochrome P4501 A in rats

摘要

摘要:
目的探讨二氧化硫(SO₂)对肝、肺微粒体细胞色素P4501A1及1A2的影响。
方法采用动式染毒技术给予雄性Wistar大鼠不同浓度SO₂染毒。采用荧光分光光度法和荧光实时定量RT-PCR方法测定各组大鼠肝、肺微粒体CYP1A1和CYP1A2活性及mRNA表达水平。
结果随着SO₂吸入浓度增加, 大鼠肝肺CYP1A1和1A2mRNA表达水平, 肝微粒体CYP1A1活性、肺微粒体CYP1A1和1A2活性逐渐降低, 且存在明显的剂量-效应关系; 肝微粒体CYP1A2活性在56 mg/m³SO₂处理组降低显著。
结论 SO₂可降低大鼠肝、肺微粒体CYP1A1和1A2活性和mRNA水平, 吸入SO₂后肝、肺对外源化合物及药物的代谢可能会受到影响。

Abstract:
Objective To study the effects of sulfur dioxide(SO₂)on hepatic and pulmonary cytochrome P4501A1 (CYP1A1)and 1A2(CYP1A2)in rats.
Methods Male Wistar rats were housed in exposure chambers and treated with different concentrations of SO₂.Fluorescence spectrophotometry was used to study the activities of CYP1A1 and 1A2.The mRNA levels of CYP1A1 and 1A2 were analyzed in livers and lungs by using a real-time reverse transcription-polymerase chain reaction(real-time RT2PCR)assay.
Results The mRNA levels of CYP1A1 and 1A2 in lungs and livers, the activities of CYP1A1 in livers and those of CYP1A1 and CYP1A2 in lungs were significantly decreased in rats exposed to SO₂ at 14 and 28 mg/m³.Furthermore, the decreases of activities and mRNA levels of these P450 enzymes caused by SO₂ at different concentrations in lungs and livers of rats followed linear dose-response curves.The hepatic CYP1A2 activities were decrased in rats exposed to SO₂ at 56 mg/m³.
Conclusion SO₂ exposure can suppress the activities and mRNA levels of CYP1A1 and 1A2 in the lungs and livers of rats.The capacity of the liver and the lung to metabolize drugs and xenobiotics can be compromised in both animals and humans.

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