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目的:探讨孕期尼古丁暴露(PNE)所致雄性子代大鼠肝脏细胞色素P450(CYP)同工酶及抗氧化酶表达和功能变化。方法:建立孕中、晚期尼古丁[2mg/(kg·d)]暴露大鼠模型,检测出生后3月和7月龄雄性大鼠肝脏CYP同工酶和抗氧化酶的表达和活性变化。结果:PNE的3月龄雄性大鼠肝脏CYP1A2、CYP2C11和CYP3A1的mRNA表达显著增加,其他亚型(CYP2A2、CYP2B1、CYP2D2和CYP2E1)为增加趋势,而CYP2E1活性显著降低,其他亚型(CYP2C6、CYP2D2/3和CYP3A1)有降低趋势;7月龄雄性大鼠肝脏CYP2A2和CYP2E1的mRNA表达增加,其他亚型(CYP1A2、CYP2C11、CYP2D2和CYP3A1)为增加趋势,而酶活性无明显变化。3月和7月龄雄性大鼠肝脏抗氧化酶谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶活性无明显改变。结论:PNE可导致雄性3月龄子代大鼠肝脏CYP同工酶的mRNA表达增加,但酶活性降低,7月龄雄性大鼠肝脏CYP同工酶功能趋于正常。提示PNE可改变雄性子代大鼠药物代谢功能但不影响抗氧化酶功能。
Objective: To investigate the changes of liver cytochrome P450 (CYP) isozymes and antioxidant enzymes in male offspring during pregnancy induced by nicotine exposure (PNE). Methods: The second and third trimester pregnant rats exposed to nicotine [2 mg / (kg · d)] were established to detect the changes of CYP isoenzymes and antioxidant enzymes in male rats’ liver at 3 and 7 months after birth. Results: The mRNA expressions of CYP1A2, CYP2C11 and CYP3A1 in the liver of 3-month-old male PNE rats were significantly increased, while the other subtypes (CYP2A2, CYP2B1, CYP2D2 and CYP2E1) were increased, while CYP2E1 activity was significantly decreased. CYP2D2 / 3 and CYP3A1). The mRNA expression of CYP2A2 and CYP2E1 in the liver of 7-month-old male rats increased. The other subtypes (CYP1A2, CYP2C11, CYP2D2 and CYP3A1) showed an increasing tendency, while the enzyme activity did not change significantly. The activity of antioxidant enzymes GSH-Px, SOD and catalase did not change significantly in male rats at 3 months and 7 months. CONCLUSION: PNE can induce the increase of liver CYP isoenzyme mRNA expression in male offspring of 3-month-old offspring, but decrease the activity of CYP isozymes in male 7-month-old offspring rats. Tip PNE can change the male offspring rat drug metabolism but does not affect the antioxidant enzyme function.