rh-EGF对恒河猴肝细胞色素P450s的影响  

Effect of rh-EGF on liver microsomal cytochrome P450s in rhesus monkey

作　　者：张呈菊[1] 马璟[1] 顾性初[1] 钱蓓丽[1] 王根宝[2] 

机构地区：[1]上海医药工业研究院毒理室,上海200437 [2]上海医药工业研究院生物部,上海200432

出　　处：《中国新药杂志》2002年第5期373-377,共5页Chinese Journal of New Drugs

摘　　要：目的 :研究重组人表皮生长因子 (recombinanthumanepidermalgrowthfactor,rh EGF)对恒河猴肝细胞色素P4 5 0s同工酶活性的影响。方法 :恒河猴口服rh EGF 16 ,32 ,16 0 μg·kg-1·d-1,qd ,连续给药 2 6周 ,于停药时及停药 8周后 ,各解剖一半动物 ,制备肝微粒体 ,进行肝细胞色素P4 5 0s总量、肝微粒体蛋白含量测定 ,用荧光分光光度法和HPLC法进行肝细胞色素P4 5 0s同工酶中 7 乙氧基试卤灵脱乙基酶 (CYP1A1)、香豆素 7 羟化酶(CYP2A6 )、甲苯磺丁脲羟化酶 (CYP2C8/ 9)、S (+) 美芬妥英羟化酶 (CYP2C19)、丁呋洛尔 1 羟化酶 (CYP2D6 )、氯唑沙宗羟化酶 (CYP2E1)比活性测定。结果 :给药 2 6周和停药 8周后 ,rh EGF对恒河猴肝细胞色素P4 5 0s总量、微粒体蛋白含量无明显影响 ,肝细胞色素P4 5 0s同工酶 (CYP1A1,CYP2A6 ,CYP2C8/ 9,CYP2C19,CYP2D6 ,CYP2E1)活性无显著变化。结论 :本试验建立的恒河猴肝细胞色素P4 5 0s测定方法快速、简便 ,可广泛用于药物开发早期以及预测药物间相互作用和药物毒性的研究等。rh EGF对恒河猴肝P4 5Objective:To study the effect of rh EGF (recombinant human epidermal growth factor,rh EGF ) on the specific activities of liver microsomal cytochrome P450s in rhesus monkey.Methods:The rhesus monkey were administered orally rh EGF for 26 weeks at 16,32 and 160 μg·kg -1 ·d -1 respectively.The recovery period was 8 weeks.The cytochrome P450s contents and liver protein content were determined by the methods of Omura and Lowry et al .Six(ethoxyresorufin O deethylase(CYP1A1),coumarin 7 hydroxylase (CYP2A6),tolbutamide hydroxylase(CYP2C8/9), S mephenytoin 4'( hydroxylase(CYP2C19),bufuralol 1'( hydroxylase (CYP2D6) and chlorzoxazone 6 hydroxylase (CYP2E1)) selective catalytic activity markers for cytochrome P450 mediated reactions were measured by spectrofluorimeter and HPLC.Results:rh EGF had no significant effect on the liver microsomal cytochrome P450s content and liver protein centent in rhesus monkey.The specific activities of CYP1A1,CYP2A6,CYP2C8/9,CYP2C19,CYP2D6 and CYP2E1 were not changed by rh EGF administration.Conclusion:rh EGF has no effect on the specific activities of P450s in rhesus monkey liver microsomes.The methods for assaying P450s activities established in this study are useful at the early stage in drug discovery and can be used to predict the drug interactions or drug toxicities.\;

关 键 词：重组人表皮生长因子 恒河猴 肝细胞色素P450s 同工酶 荧光分光光度法 高效液相色谱法 

分 类 号：R977.6[医药卫生—药品]