妊娠状态下大鼠肝脏外源物代谢功能的改变

Changes of Hepatic Xenobiotic-Metabolic Functions in Pregnant Rats

目的:观察妊娠状态下大鼠肝脏外源物代谢相关酶活性的变化,探讨其可能带来的临床意义。方法:雌性大鼠分为未受孕和受孕(妊娠21d)两组。测定两组大鼠肝脏外源物代谢相关酶(包括Ⅰ相酶、Ⅱ相酶和抗氧化酶)活性。结果:受孕组大鼠肝微粒体Ⅰ相酶——细胞色素P450(CYP450)1A1、1A2、1B1、2B1、2E1和3A活性分别下降至未孕组的62.3%(P<0.01)、43.8%(P<0.01)、75%(P<0.05)、80%、64.6%(P<0.05)和87.8%,而Ⅱ相酶葡萄糖醛酸转移酶(UGT)和谷胱甘肽S-转移酶(GST)活性分别增加至未孕组的1.23倍(P<0.05)和1.17倍(P<0.05)。受孕组大鼠肝细胞质超氧化物歧化酶(SOD)活性增加至未孕组的1.31倍(P<0.01),而谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(Cat)活性下降至未孕组的81.2%(P<0.01)和47.5%(P<0.01)。谷胱甘肽还原酶(GSH-Re)活性没有显著差异。结论:妊娠状态下,大鼠肝脏外源物代谢酶活性均发生变化。这些酶活性改变可能是母体对妊娠时期机体生理学变化的一种适应性保护作用,该变化将影响妊娠母体的药物代谢能力及临床疗效。

Objective： To observe the alteration of hepatic xenobiotic-metabolic enzymes activities in pregnant rats, and to explore its possible significances in clinic. Methods： Female rats were divided into non-pregnancy and pregnancy （21st gestation day） groups. The animals were sacrificed and the maternal livers were removed. Activities of drug-metabolizing and antioxidative enzymes were monitored. Results： Compared with the non-pregnancy group, the activities of cytochrome P450 （CYP450）1A1, 1A2, 1B1, 2B1, 2E1 and 3A in hepatic microsomes of pregnancy group were 62.3% （P〈0.01）, 43.8M （P〈0.01）, 75%o （P〈0. 05）, 80%, 64.6% （P〈0.05） and 87.8% of those in non-pregnancy group rats, respectively. The activities of maternal hepatic UDP glucuronosyltransferase （UGT） and glutathione S-transferase （GST） in pregnancy group were 1. 17- and 1.23-fold （P〈0.05） of those in non-pregnancy group, respectively. In pregnant group, the activity of superoxide dismutase （SOD） increased to 1.31-fold （P〈0. 01）, whereas the activities of glutathione peroxidase （GSH-Px） and catalase （Cat） decreased to 81.2% （P〈0. 01） and 47.5% （P（0.01）, and the activities of glutathione reduetase （GSH-Re） had no significant change when compared with that in non-pregnancy group. Conclusion： In pregnant rats, the activities of xenobiotic-metabolic enzymes in maternal liver changed. The variation of these enzyme activities may be a biologically protective response to the physiologic changes in pregnancy. Meanwhile, these changes will probably influence maternal metabolizing functions and therapeutic effects of drugs.