丝裂霉素C在体外和体内对大鼠肝脏CYP2D1/2 ,CYP2C11和CYP1A2活性的影响(英文)  

Effect of in vitro and in vivo treatment with mitomycin C on activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver

作　　者：郝福荣[1] 严敏芬[1] 童顺高[1] 许立明[1] 金一尊[1] 

机构地区：[1]复旦大学放射医学研究所,上海200032

出　　处：《药学学报》2004年第11期897-903,共7页Acta Pharmaceutica Sinica

基　　金：NationalNaturalScienceFoundationofChina(3 0 10 0 0 42 ) .

摘　　要：目的　研究丝裂霉素C(MMC)在体外和体内对大鼠肝脏CYP2D1 2 ,CYP2C11和CYP1A2活性的影响。方法　用诱导剂和抑制剂分别在体内和体外调节大鼠肝脏P4 5 0同工酶活性 ,并用HPLC检测 3种同工酶各自底物的特定代谢产物 ,以计算同工酶活性。结果　在体外 ,MMC可以使地塞米松诱导的大鼠肝脏微粒体CYP2D1 2 ,CYP2C11和CYP1A2活性分别抑制 (19± 6 ) % (P <0 0 5 ) ,(85± 10 ) % (P <0 0 1)和 (36± 6 ) % (P <0 0 5 ) ,并使 β 萘黄酮诱导的CYP1A2活性降低 (5 8± 6 ) % (P <0 0 1)。在体内 ,以 2 0 %LD50 的剂量连续 3d或 6d腹腔注射MMC对大鼠肝脏CYP2D1 2 ,CYP2C11和CYP1A2活性的影响无统计学差异。结论　在体外MMC可以抑制大鼠肝微粒体CYP2D1 2 ,CYP2C11和CYP1A2的活性 ,但在体内对这 3种细胞色素P4 5 0同工酶活性的影响无统计学差异。Aim To evaluate the effect of in vitro and in vivo treatment with mitomycin C (MMC) on activities of CYP2D1/2, CYP2C11, and CYP1A2 in the liver of male rats. Methods Using HPLC to determine the activities of the three isoenzymes in rat liver microsomes by detecting the specific metabolites of their substrates after treatment with inducers in vivo or inhibitors in vitro. Results In vitro, MMC inhibited the activity of CYP2D1/2, CYP2C11, and CYP1A2 in dexamethasone-induced microsomes by (19±6)% ( P<0.05), (85±10)% ( P<0.01), and (36±6)% ( P<0.05), respectively, and decreased the activity of CYP1A2 in β-naphthoflavone-induced microsomes by (58±6)% ( P<0.01). Rats were injected intraperitoneally with 20% of the LD 50 of MMC for 3 or 6 d. The treatment showed no significant effect on microsomal activities of CYP2D1/2, CYP2C11 or CYP1A2. Conclusion MMC can inhibit the activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver microsomes in vitro, but it showed no significant effect on the activities of the three isoenzymes in vivo.

关 键 词：丝裂霉素C 细胞色素P450 诱导剂 抑制剂 肝微粒体 

分 类 号：R979.11[医药卫生—药品] R968.1[医药卫生—药学]