CAJ | 학술논문

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P450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＜0.05),(85±10)%(P＜0.01)和(36±6)%(P＜0.05),并使β-萘黄酮诱导的CYP1A2活性降低(58±6)%(P＜0.01).在体内,以20%LDso的剂量连续3 d或6 d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P450同工酶活性的影响无统计学差异.
목적연구사렬매소C(MMC)재체외화체내대대서간장CYP2D1/2,CYP2C11화CYP1A2활성적영향.방법용유도제화억제제분별재체내화체외조절대서간장P450동공매활성,병용HPLC검측3충동공매각자저물적특정대사산물,이계산동공매활성.결과재체외,MMC가이사지새미송유도적대서간장미립체CYP2D1/2,CYP2C11화CYP1A2활성분별억제(19±6)%(P＜0.05),(85±10)%(P＜0.01)화(36±6)%(P＜0.05),병사β-내황동유도적CYP1A2활성강저(58±6)%(P＜0.01).재체내,이20%LDso적제량련속3 d혹6 d복강주사MMC대대서간장CYP2D1/2,CYP2C11화CYP1A2활성적영향무통계학차이.결론재체외MMC가이억제대서간미립체CYP2D1/2,CYP2C11화CYP1A2적활성,단재체내대저3충세포색소P450동공매활성적영향무통계학차이.
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/3-naphthoflavone-induced microsomes by (58 ± 6) % (P ＜ 0. 01 ).Rats were injected intraperitoneally with 20% of the LD50 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.