Hill M D, Abramson F P
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Res Commun Chem Pathol Pharmacol. 1990 Jul;69(1):33-48.
The effects of phenobarbital (PB) and dexamethasone (DX) on maternal and fetal hepatic cytochrome P450 content, benzphetamine (BzP) demethylation activity, the plasma concentration of alpha 1-acid glycoprotein (AGP), and the binding of propranolol (PPL) were examined in guinea pigs. In maternal guinea pigs, PB increased AGP-specific PPL binding by 131%, P450 by 94%, and BzP demethylation by 261%. DX only increased maternal AGP-specific PPL binding (122%). In fetal guinea pigs, neither PB nor DX resulted in significant increase for any of these parameters. The combination of PB and DX synergistically increased fetal P450 content (153% increase) and BzP demethylation (84% increase). In contrast, this combination treatment did not increase maternal P450 and BzP demethylation to a greater extent than by PB treatment alone nor did it increase the binding of PPL in PCA-treated fetal plasma. The synergy of P450 induction found in the fetus implicates glucocorticoids as important regulators of fetal hepatic microsomal enzyme maturation.
在豚鼠中研究了苯巴比妥（PB）和地塞米松（DX）对母体和胎儿肝脏细胞色素P450含量、苄非他明（BzP）去甲基化活性、α1-酸性糖蛋白（AGP）血浆浓度以及普萘洛尔（PPL）结合的影响。在母豚鼠中，PB使AGP特异性PPL结合增加131%，P450增加94%，BzP去甲基化增加261%。DX仅增加母体AGP特异性PPL结合（122%）。在胎豚鼠中，PB和DX均未使这些参数中的任何一项显著增加。PB和DX联合使用可协同增加胎儿P450含量（增加153%）和BzP去甲基化（增加84%）。相比之下，这种联合治疗并未比单独使用PB治疗更显著地增加母体P450和BzP去甲基化，也未增加PCA处理的胎儿血浆中PPL的结合。在胎儿中发现的P450诱导协同作用表明糖皮质激素是胎儿肝脏微粒体酶成熟的重要调节剂。
