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

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(GSH-Px)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。

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

AIM: To evaluate the alterations of ma-ternal hepatic drug-metabolizing enzymes and antioxidative function in tobacco-induced intrauterine growth retardation(IUGR).METHODS: Pregnant rats were assigned to control grouPand tobacco group.IUGrmodel was pro-duced 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,littersize and placental weights were recorded.Subcelluarfractionsof liverwere prepared by differential centrifuga-tion.Activities of drug-metabolizing and antioxidative enzymes were monitored.RESULTS: In the tobacco ex-posure group,fetal body weights,littersize and placental weights were significantly reduced(P<0.01).The levels of cytochrome P450(CYP)1A1 in hepatic micro-somes increased by 37.9%,and the activities of CYP3A and 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 alter-ations of partial drug-metabolizing enzymes and antioxida-tive function in maternal liver,and these changes may play an important role in inducing IUGR.Meanwhile,to-bacco exposure in pregnancy may change the drug efficacy and increase the drug toxicity.