大鼠肝脏微粒体中3种细胞色素P-450同工酶活性研究  

Studies on 3 Isoenzymes Activities of Cytochrome P-450 in Rat Liver Microsomes

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

出　　处：《复旦学报（医学版）》2004年第4期354-358,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金 (3 0 10 0 0 42 )资助项目

摘　　要：目的　研究大鼠肝脏微粒体中CYP2D1/ 2、CYP2C11、CYP1A2 3种细胞色素P 4 5 0同工酶的活性。方法　用诱导剂和抑制剂分别在体内和体外调节大鼠肝脏P 4 5 0同工酶活性 ,并用高效液相法检测同工酶底物的特异性代谢产物来计算同工酶活性。结果　 3种同工酶底物的特异性代谢产物的分离度达到了 1.5 ;天内、天间精密度均小于 10 .2 2 % ,天内、天间准确度均小于 14 .95 % ;相关系数都达到 0 .999。在体内腹腔注射地塞米松能使CYP1A2、CYP2D1/ 2、CYP2C11活性分别增加 1.3倍 (P <0 .0 5 )、1倍 (P <0 .0 1)和 2 .3倍 (P <0 .0 1)。β 萘黄酮可使CYP1A2活性增加 13.7倍 (P <0 .0 1)。在体外 ,呋拉茶碱可以不同程度地抑制CYP1A2、CYP2C11活性 ;普罗地芬、α 萘黄酮可以抑制CYP1A2活性 ;奎宁可以抑制CYP2D1/ 2活性。结论　甲苯磺丁脲、右美沙芬和非那西汀可以作为人体的探药 ,因而实验建立的方法有望用于检测人血浆或尿液中 3种探药的特定代谢产物 ,分别用于估测人肝脏CYP2C9、CYP2D6和CYP1A2的活性。Purpose: To study the interactions between Cytochrome P-450 and drug metabolism or drug-drug interactions, the activity of CYP2D1/2input commas CYP2C11input commas CYP1A2 in rat liver microsomes was determined by HPLC. Methods: The activities of the three isoenzymes were determined by detected the specific metabolites of their substrates by HPLC after treated by induers in vivo or inhibitors in vitro. Results: The specific metabolites of substrates of CYP2C11input commas CYP1A2 and CYP2D1/2, were separated and the degrees of separation was reached up to 1.5; Interday and intraday accuracies were within 10.22%, Interday and intraday precisions were less than 14.95%. The correlation coefficients were 0.999. In vivo, DEX injected to rats intraperitoneally can increased the activities of CYP2D1/2input commas CYP2C11input commas CYP1A2 in rat liver microsoemes by 1 (P< 0.01)input commas 2.3 (P < 0.01) and 1.3 times (P < 0.05), respectively, β-NF can increased the activities of CYP1A2 13.7 times P < 0.01). In vitro, Fur can inhibited the activities of CYP2C11 and CYP1A2 to different extents; SKFinput commas α-NF can decreased the activity of CYP1A2;Que can inhibited the activity of CYP2D1/ 2. Conclusions: DMPinput commas TBA and PAC can also use as human probes, it is possible to determine the activities of three isoenzymes by detecting the specific metabolism in human plasma or urine.

关 键 词：细胞色素P-450 同工酶活性 诱导剂 抑制剂 

分 类 号：Q559[生物学—生物化学]