吸烟所致宫内发育迟缓孕鼠肝脏药物代谢酶及抗氧化酶活性的变化  

Alterations of maternal hepatic drug-metabolizing and antioxidative enzymes in tobacco-induced intrauterine growth retardation in rats

作　　者：王婷[1] 汪晖[1] 汤宏斌[2] 鄢友娥[1] 曾汉高[1] 

机构地区：[1]武汉大学基础医学院药理学系 [2]武汉大学实验动物中心

出　　处：《中国临床药理学与治疗学》2005年第11期1245-1248,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖北省计生委青年基金项目(№2003)

摘　　要：目的:研究和探讨吸烟所致宫内发育迟缓(IUGR)大鼠母体肝脏药物代谢酶活性和抗氧化功能的改变及其所带来的毒理学和药理学意义。方法:妊娠天数明确的Wistar大鼠16只,分为对照组和吸烟组。采用吸烟法建立大鼠IUGR模型,孕21d剖腹取胎,测量胎鼠生长发育指标(体重、身长、尾长)和胎盘重。差速离心法制备孕鼠肝亚细胞组分,测定多种药物代谢酶和抗氧化酶活性。结果:IUGR大鼠胎仔平均体重、身长、尾长、胎盘重都明显低于对照组,分别为对照组的87.7%、94.5%、95.3%和83.0%(P<0.01)。母体肝脏微粒体细胞色素P450(CYP)1A1活性升高,为对照组的137.9%(P<0.05);而CYP3A活性降低,为对照组的73.3%(P<0.05),谷胱甘肽S转移酶(GST)活性也降低,为对照组的86.5%(P<0.05)。母体肝脏胞浆超氧化物歧化酶(SOD)和过氧化氢酶(Cat)活性降低(P<0.05);谷胱甘肽过氧化物酶(GSHPx)活性升高,为对照组的1.11倍(P<0.05)。结论:孕期吸烟可致IUGR大鼠母体肝脏部分药物代谢酶活性和抗氧化系统功能改变,这些改变可能是导致IUGR发生的原因之一,同时吸烟可能改变孕期用药的疗效,增加药物毒性。AIM： To evaluate the alterations of maternal hepatic drug-metabolizing enzymes and antioxidative function in tobacco-induced intrauterine growth retardation （IUGR）. METHODS： Pregnant rats were assigned to control group and tobacco group. IUGR model was produeed by smoking from gestational days （GD） 9 to GD 20. Fetuses were removed by laparotomy on GD 21. The fetal development parameters such as fetal body weights, litter size and placental weights were recorded. Subeelluar fractions of liver were prepared by differential centrifuga- tion. Activities of drug-metabolizing and antioxidative enzymes were monitored. RESULTS： In the tobacco ex- posure group, fetal body weights, litter size and placental weights were significantly reduced （ P 〈 0.01 ）. The levels of cytochrome P450 （CYP） 1A1 in hepatic microsomes increased by 37.9%, and the activities of CYP3Aand glutathione S-transferase （GST） decreased to 73.3 % and 86.5 % when compared to control group. Meanwhile, the activities of superoxide dismutase （SOD） and catalase （Cat） decreased to 81.0% and 79.7%, respectively, whereas the activity of glutathione peroxidase （GSH-Px） increased in comparison with control group. CONCLUSION：Tobacco exposure in pregnancy results in the alterations of partial drug-metabolizing enzymes and antioxidative function in maternal liver, and these changes may play an important role in inducing IUGR. Meanwhile, tobacco exposure in pregnancy may change the drug efficacy and increase the drug toxicity.

关 键 词：吸烟 胎儿宫内发育迟缓 母体肝脏 药物代谢酶 抗氧化酶 

分 类 号：R965.1[医药卫生—药理学]