孕期尼古丁暴露所致成年雄性子代大鼠肝脏CYP同工酶及抗氧化酶变化  

Effects of Prenatal Nicotine Exposure on Hepatic CYP Isozymes and Antioxidative Enzymes in Male Adult Offspring Rats

作　　者：何靓[1] 郭喻[1] 李镜清 纪振宇[1] 黄民[2] 汪晖[1] 

机构地区：[1]武汉大学基础医学院药理学系,湖北武汉430071 [2]中山大学药学院临床药理研究所,广东广州510080

出　　处：《武汉大学学报（医学版）》2016年第1期15-19,24,共6页Medical Journal of Wuhan University

基　　金：国家自然科学基金项目(编号:81220108026;81430089;81473290)

摘　　要：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 effect of prenatal nicotine exposure（PNE）on the expression and activities of hepatic CYP isozymes and antioxidative enzymes in different periods of male adult offspring rats.Methods：PNE rat model was established to detect the mRNA expression and activities of hepatic CYP isozymes and antioxidative enzymes in 3-month-and 7-month-old male offspring rats.Results：In 3-month-old male offspring of PNE,the mRNA expression of hepatic CYP1A2,CYP2C11 and CYP3A1increased and the other CYP isoforms showed an increasing trend.The activity of CYP2E1 decreased and the other CYP isoenzymes showed a decreasing trend.In 7-month-old male offspring,the mRNA expression of hepatic CYP2A2 and CYP2E1increased and the other isoforms showed an increasing trend while the activities did not change sig-nificantly.There was no significant change in the activities of hepatic antioxidative enzymes glutathione peroxidase（GSH-Px）,superoxide dismutase（SOD）and catalase（CAT）in 3-monthand 7-month-old male offspring.Conclusion：PNE can lead to an increase of mRNA expression but a decrease of activitioes of hepatic CYP isozymes in young male offspring rats.The function of hepatic CYP isozymes tends to be normal in 7-month-old male offspring rats,which suggests that PNE may change drug-metabolic function but does not affect antioxidative function in adult male offspring rats.

关 键 词：尼古丁 大鼠 细胞色素P450同工酶 抗氧化酶 

分 类 号：R994.4[医药卫生—毒理学]