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作 者:王莹[1,2] 王全军[2] 吴纯启[2] 施畅[2] 王青秀[2] 廖明阳[2]
机构地区:[1]辽宁医学院药物研究所,辽宁锦州121002 [2]军事医学科学院毒物药物研究所,国家北京药物安全评价研究中心,北京100850
出 处:《中国新药杂志》2008年第19期1668-1670,1675,共4页Chinese Journal of New Drugs
摘 要:目的:观察Z24对大鼠肝脏CYP450酶系的影响。方法:雌性Wistar大鼠,灌胃(ig)给予Z24(0,50,100,200 mg.kg-1.d-1),连续5 d,以0.9%氯化钠溶液作对照,末次给药后次日,处死大鼠,测定肝微粒体中CYP450总含量、细胞色素b5(Cyt-b5)含量、NADPH-CYP450还原酶活性以及1A2,1B1,2E1,3A4亚型活性。结果:与对照组相比,各剂量组CYP450总含量、NADPH-CYP450还原酶活性及CYP1B1、2E1亚型活性均明显升高(P<0.05);100和200 mg.kg-1组Cyt-b5含量升高(P<0.05);200 mg.kg-1组CYP1A2和3A亚型活性升高(P<0.05)。结论:Z24对CYP450、NADPH-CYP450还原酶及CYP1B1、2E1亚型有诱导作用,剂量达100和200 mg.kg-1时分别对Cyt-b5和CYP1A2、3A亚型产生诱导作用。Objective: To investigate the effect of Z24 on the contents and activities of cytoehrome P450 (CYP450) system in rat liver. Methods: In female Wistar rats, Z24 (50, 100 and 200 mg·kg^-1 ) or saline (control) was intragastrically administrated for 5 days. Then, total contents of CYP450 and cytoehrome b5, and activities of NADPH-CYP450 reductase and the subtypes CYP1A2,1B1,2E1 ,3A in liver microsome were detected. Results: Total CYP450 contents, activities of NADPH-CYP450 reductase and subtype CYP1B1, 2E1 were higher in all three Z24 groups than in control group. Cytoehrome b5 content increased in Z24 100 and 200 mg·kg^-1 groups (P〈0.05), and the activities of subtypes CYP1A2 and CYP 3A increased in Z24 200 mg·kg^-1 group (P 〈 0.05) Conclusion: CYP450, NADPH-CYP450 reductase and subtypes CYP1B1, 2E1 can be induced by Z24. Cytochtome, b5. and subtypes 1A2 and 3A can also be induced by Z24 at 100 and 200 mg.kg^-1
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