银杏叶提取物对AFB1诱发大鼠肝癌过程中CYP3A4活性的影响

Effects of Ginkgo Extract on the Activity of CYP4A4 during Hepatocarcinogenesis Induced by AFB1 in Wistar Rats

目的动态观察银杏叶提取物(Ginkgo biloba extract,EGb761)在黄曲霉毒素B1(AFB1)诱发大鼠肝癌过程中对肝组织代谢酶CYP3A4活性的影响。方法将70只4周龄Wistar雄性大鼠随机分为3组:AFB1组(25只),AFB1+EGb761组(25只)及对照组(20只)。在诱发肝癌过程中,分别于第13,23,33,43,53,63周对大鼠进行肝活检;实验至第73周处死全部动物取肝组织;利用大鼠肝组织微粒体混合酶体外代谢体系,采用荧光分光光度定量法动态检测肝标本中CYP3A4酶代谢活性。结果 AFB1+EGb761组肝癌发生率明显低于AFB1组(P<0.01),而对照组为无肿瘤发生。各组肝组织CYP3A4活性在第23周和第53周呈现双波峰变化;AFB1+EGb761组在第53周和第63周时CYP3A4酶活性低于AFB1组,差异有统计学意义(P<0.05)。结论 EGb761可显著降低AFB1诱发大鼠肝癌的发生率。其机制之一可能为抑制大鼠肝组织CYP3A4活性从而减少前致癌物的代谢,降低AFB1致癌性及其化学性肝损伤达到保护肝脏的作用。

Objective To investigate the effects of Ginkgo giloba extract（extract 761 from Ginkgo giloba,EGb761）on the activity of CYP3A4 during hepatocarcinogenesis induced by aflatoxin B1（AFB1） in wistar rats. Methods Seventy Wistar rats were randomly divided into 3 groups： AFB1 group（25）,AFB1＋EGb761 group（25） and control group（20）.During hepatocarcinogenesis,liver biopsies were performed on all animals in 13th-,23rd-,33rd-,43rd-,53rd-and 63rd-week of the experiment.Animals were sacrificed in the 73rd-week and liver tissues were collected.Using the hepatic microsomal mixed-function oxidase enzyme system,the activity of CYP3A4 was dynamically examined in liver samples by quantitative fluorescence spectrophotometry. Results The incidence of hepatocellular carcinoma（HCC） in AFB1＋EGb761 group was significantly lower than that in AFB1 group（P〈0.01）.No hepatocellular carcinoma developed in control group.In the whole experiment process,the CYP3A4 metabolic enzymes activity shows double peaks in each groups with dynamic observation.The activity of CYP3A4 in AFB1＋EGb761 group was significantly lower than that in AFB1 group in 53rd-and 63rd-week（P〈0.05）. Conclusion The Ginkgo biloba extract（EGb761） can effectively inhibit the occurrence of hepatocellular carcinoma induced by AFB1.The activity of CYP3A4 can be inhibited during hepatocarcinogenesis in AFB1＋EGb761 groups.The mechanism of treatment may be due to the decrease of carcinogens metabolic and that reduce carcinogenicity and hepatic injury of chemical to attain the role of protect liver.