CYP3A4活性变化在金花茶抑制AFB1诱发大鼠肝癌过程中的意义.pdfVIP

第十一届中南地区实验动物科技交流会论文集 on all animals at 13th-, 23rd-, 33rd-, 43rd-, 53rd- and 63rd-week of the experiment. Animals were sacrificed at the 73rd-week and liver tissues were collected. Using the hepatic microsomal mixed-function oxidase enzyme system, the CYP3A4 activity was dynamically examined in liver samples by quantitative fluorescence spectrophotometry. Results The CYP3A4 activity in both groups had different levels of changes. In the whole experiment process, The CYP3A4 metabolic enzymes activity show increased gradually with peak value at the 23rd-week and then decreased gradually, in each groups with dynamic observation. And the CYP3A4 activity increased again at the 53rd-week, forming double peaks. CYP3A4 activities decreased significantly during53rd- and 63rd-week in AFB1 and CCT group compared to control group (P＜0.05). The level of CYP3A4 activity in control group was decreased at the 33rd-week and 63rd-week, and no change significantly in other stage.Conclusion The CYP3A4 activity was inhibited during hepatocarcinogenesis in CCT groups. This may be due to decrease of carcinogens metabolic and that reduce carcinogenicity and hepatic injury of chemical to attain the role of protect liver. 【Key words 】 Cytochrome P450 3A4; Aflatoxin B1; Hepatocellular Carcinoma; The Camellia chrysantha （Hu ）Tuyama (CCT) 黄曲霉毒素B （AFB ）是被世界卫生组织确定的人类第一类已知致癌物，它必须通过 1 1 体内的生物转化形成活性中间体AFB -8,9-环氧化物（AFB -8,9-epoxide，AFBO ）才具有致 1 1 癌性[1] 。肝微粒体细胞色素CYPs是一组结构和功能相关的超家族基因编码的同工酶,负责外 源性和内源性物质及许多其他合成性化学物质的代谢和生物转化，在解毒和生物活化中起着 重要作用。它可以被某些化合物诱导或抑制,影响其生物活性和毒性。AFB1的代谢作用在肝 脏中发生，主要是通过CYPs超家族成员经氧化作用形成几种亲电子的中间代谢物[2] 。CYPs 超家族成员介导AFB1代谢活化和解毒的药物代谢酶主要有CYP2E1、CYP3A4 等几种亚族 [3] 。有关AFB 诱发大鼠肝癌与CYP3A4活性的影响目前尚未见报道。本研究采用大鼠肝微粒 1 体混合酶体外代谢体系，利用荧光分光光度定量法动态检测AFB1诱发肝癌过程中不同时期 CYP3A4酶代谢活性，初步评估金花茶抑制AFB1诱发肝癌过程中CYP3A4酶活性在致癌过程 中的意义。 1 材料与方法