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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 5 0s部分同工酶无影响
OBJECTIVE: To study the effect of recombinant human interleukin growth factor (rh EGF) on the cytochrome P450 isoenzyme activity of hepatocytes in rhesus monkeys. Methods: The rhesus monkeys were orally administrated with rh EGF 16, 32, 160 μg · kg-1 · d-1, qd for 26 weeks continuously. Half of the animals were each anatomized at the time of withdrawal and 8 weeks after discontinuation, Liver microsomes, the total amount of liver cytochrome P450s, liver microsomal protein content determined by fluorescence spectrophotometry and HPLC method of liver cytochrome P450 isoenzyme 7 ethoxylate resorulent deethylation (CYP1A1), coumarin 7 hydroxylase (CYP2A6), tolbutamide hydroxylase (CYP2C8 / 9), S (+) mephenytoin hydroxylase (CYP2C19) (CYP2D6), zoledronic acid hydroxylase (CYP2E1) specific activity assay. RESULTS: After 24 weeks of treatment and 8 weeks of withdrawal, rh EGF had no significant effect on the total amount of cytochrome P450s and the content of microsomal proteins in rhesus monkeys. The cytochrome P450 isozymes (CYP1A1, CYP2A6 , CYP2C8 / 9, CYP2C19, CYP2D6, CYP2E1) activity did not change significantly. Conclusion: The method for determination of cytochrome P450s in Rhesus monkey established in this study is rapid and simple, and can be widely used in the early stage of drug development and the prediction of the drug interactions and drug toxicity. rh EGF did not affect the partial isozymes of liver P450s in rhesus monkeys