非那西丁在二乙基亚硝胺诱发肝癌大鼠的代谢  

The metabolism of phenacetin in the rats with diethylnitrosamine induced hepatoma

作　　者：崔贞福[1] 张国庆[2] 罗明[1] 王华梁[3] 王健[3] 阎振林[1] 贺平[1] 钱其军[1] 吴孟超[1] 郭亚军[1] 

机构地区：[1]第二军医大学东方肝胆外科医院肿瘤免疫基因治疗中心,上海200438 [2]第二军医大学东方肝胆外科医院药械科,上海200438 [3]第二军医大学东方肝胆外科医院检验科,上海200438

出　　处：《中国药理学通报》2000年第2期202-204,共3页Chinese Pharmacological Bulletin

摘　　要：目的　①研究非那西丁在二乙基亚硝胺 (DEN)诱发肝癌大鼠中的代谢 ,以及其它评估肝脏功能指标的改变 ;②血浆结合型代谢产物含量改变对非那西丁试验的影响。方法　饮用DEN诱发大鼠肝癌 ,观察血液非那西丁及利多卡因代谢产物 ,白蛋白和胆红素含量 ,凝血酶原时间的改变 ;采用HPLC法测定血浆中非那西丁结合型和游离型代谢产物含量。结果　与正常对照组相比 ,DEN组大鼠肝脏出现多发性癌结节 ,肝 /体重比增加 3 3倍 ,血浆谷丙转氨酶、γ 谷氨酰转肽酶和碱性磷酸酶含量明显升高 ,但凝血酶原时间、血浆白蛋白、非那西丁和利多卡因代谢产物含量无明显改变。DEN组大鼠血浆非那西丁游离型代谢产物含量高于正常对照组 43 9% (P <0 0 1) ,但结合型 +游离型代谢产物总量无明显差别。结论　在DEN诱发肝癌大鼠 ,肝细胞严重受损 ,肝脏体积增大 ,非那西丁代谢等肝功能试验无明显改变。同时测定游离型及结合型代谢产物含量 ,才能正确反映肝脏的生物转化功能。AIM To investigate ① the metabolism of phenacetin in the rats with diethylmitrosamine (DEN) induced hepatoma and the changes of other indexes for accessing the liver function; ② the influence of combined metabolite contents on the phenacetin trials. METHODS Hepatoma was induced in rats with DEN added in the drinking water. The changes of phenacetin and lidocaine metabolite contents in blood, albumin and bilirubin level, and prothrombin time were documented. The free and combined metabolites of phenacetin in plasma were assayed with HPLC. RESULTS The multifocal carcinomas presented in the liver of the rats in DEN group and the ratio of liver/body weight increased 3 3 times with significant increase of plasma glutamyl pyruvic acid transaminase,γ glutamyl transpeptidase and alkaline phosphatase levels, while the prothrombin time, plasma albumin and phenacetin and lidocaine metabolites did not change significantly. The free type phenacetin metabolites in plasma was higher in DEN group than in normal control group by 43 9% (P<0 01), while the total level of free type plus combined type metabolites changed little. CONCLUSION Liver cells were damaged severely in the rats with DEN induced hepatoma. The liver mass increased without any significant changes in the liver function tests as phenacetin metabolites. Simultaneous assay of free and combined type metabolites can reflect the biotransformation function of liver corroctly.

关 键 词：肝癌 非那西丁 利多卡因试验 DEN 

分 类 号：R735.7[医药卫生—肿瘤] R921.1[医药卫生—临床医学]