摘要
目的 探讨乙醇对小鼠肝脏细胞色素 P4 5 0 3A同工酶 -红霉素 N -脱甲基酶活性的影响。方法 每天小鼠经口灌胃给予不同剂量的乙醇 ,连续给药 4 d、14 d、2 1d和 2 8d,末次给药后不同时点 (6 h、12 h、18h或 2 4 h)剖杀动物取肝脏组织 ,用钙沉淀法制备肝脏微粒体 ,Nash法检测红霉素 N-脱甲基酶 (ENRD)活性。结果 经口灌胃给予不同剂量的乙醇 ,连续给药 4 d后小鼠肝脏微粒体 ENRD活性显著上升 ,并呈明显的剂量 -效应关系 ,但无明显的性别差异。给药时间长短不同 ,乙醇对小鼠肝脏微粒体 ERND活性的影响有明显差异 ;连续给药 4 d至 14 d,乙醇对小鼠肝脏ERND活性的影响最明显 ,但随着给药时间的延长 ,乙醇对小鼠肝脏 ERND活性的影响逐渐减弱。在末次给药后 12 h,肝脏微粒体 ERND活性最高 ;末次给药后 18h仍维持较高水平 ;末次给药后2 4 h,雌性小鼠肝脏微粒体 ERND仍维持较高水平 ,而雄性小鼠肝脏 ERND活性则明显下降。结论 在体内条件下 ,乙醇明显升高小鼠肝脏细胞色素 P4 5 0 3A同工酶 -红霉素 N
Objective To explore the effects of ethanol on erythromycin N-demethylase (ERND) in mouse liver. Methods Mice were orally given different doses of ethanol for 4, 14, 21 and 28 d. Mice were sacrificed at 6, 12, 18 and 24 h after last administration. Mouse livers were excised for microsome isolation. Erythromycin N-demethylase (ERND), a cytochrome P450 3A isoform, catalytic activity was measured with Nash method. Results ERND catalytic activity significantly increased in a dose-dependent manner in mice which were orally administered ethanol for 4 or 14 days. Ethanol-induced ERND catalytic activity reached the peak at 12 h after last ethanol administration, lasted at least 18 h and weakened at 24 h. However, ERND catalytic activity increased a little in chronically ethanol-treated mice. Conclusions Ethanol increased the in vivo ERND catalytic activity in mouse liver.
出处
《疾病控制杂志》
2004年第2期102-105,共4页
Chinese Journal of Disease Control and Prevention
基金
国家自然科学基金 (30 3716 6 7)
