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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。
Objective To study the effects of mitomycin C (MMC) on the activity of CYP2D1 2, CYP2C11 and CYP1A2 in rat liver in vitro and in vivo. Methods Inducers and inhibitors were used to regulate the hepatic P450 isoenzyme activity in vivo and in vitro. The isoenzymes activities of the isoenzymes were assayed by HPLC. Results In vitro, MMC inhibited dexamethasone-induced CYP2D1 2, CYP2C11 and CYP1A2 activities in rat liver microsomes by (19 ± 6)% (P <0 05) and (85 ± 10)% (P <0.01) and (36 ± 6)% (P <0 05), respectively, and decreased β-naphthoflavone induced CYP1A2 activity by 58 ± 6% (P <0.01). There was no significant difference in the activity of CYP2D1 2, CYP2C11 and CYP1A2 in rat livers after intraperitoneal injection of MMC at a dose of 20% LD50 for 3 or 6 days. Conclusion MMC can inhibit the activity of CYP2D1 2, CYP2C11 and CYP1A2 in rat liver microsomes in vitro. However, there is no significant difference in cytochrome P450 isoenzyme activity in vivo.