银杏叶提取物对黄曲霉毒素B_1诱导的大鼠肝癌的化学预防作用

摘要

Objective To investigate the preventive effect of Ginkgo biloba extract (EGb 761) on hepatocarcinogenesis induced by aflatoxin B_1 (AFB_1) and the mechanism of its antitoxident activity. Methods Seventy-one Wistar rats were divided into at random three groups: group A (AFB_1), group B (AFB_1 + EGb761) and group C (control). The animals in groups A and B were injected with AFB_1 (ip, 100-200 μg/kg body weight, 1-3 times/week). The rats in group B were fed on the food containing EGh761, but thos in groups A and C were fed on the normal food. Liver biopsies were performed on all rats at the 14th, 28th and 42nd week of the experiment, and the animals were sacrificed at the 64th week. Histopathological changes of the liver tissues and the levels of malondialdebyde (MDA) were examined, and the protein expression of 8-hydroxydeoxyguanosine (8-OHdG) was detected by immunohistochemistry staining. Results The incidence of hepatocellular carcinoma (HCC) in group B (26.92%) was significantly lower than that in group A (76.00%) (P<0.01). None HCC developed in group C. The level of MDA in rat's liver tissues in group B was significantly lower than that in group A at four time points (P<0.05), and also significantly lower than that in group C at the 64th week (P<0.05). The expression of 8-OHdG protein in rat liver tissues collected at the week of 28, 42 and 64 in group B was significantly lower than that in group A (P<0.05). Conclusion The extenuation of lipid peroxidation and the inhibition of the expression of 8-OHdGprotein are the potential mechanisms for the chemopreventive effects of EGb761.%目的 探讨银杏叶提取物(EGb761)对黄曲霉毒素B_1(AFB_1)致大鼠肝癌(HCC)发生发展的干预作用及其机制.方法 A组(AFB_1组28只)、B组(AFB_1+EGb761组29只)和C组(对照组14只)3组大鼠,定期肝活检并于第64周全部处死,观察实验肝癌发生过程中大鼠肝组织病理学、肝癌发生率、丙二醛(MDA)及8-羟基鸟嘌呤核苷(8-OHdG)蛋白表达的变化.结果 B组大鼠诱癌各时期肝脏损害均较A组轻,增生性病变发生亦较迟,肝癌诱发率(26.92%)明显低于A组(76.00%)(P<0.01),对照组无肿瘤发生.在各检测点(实验第14、28、42、64周),B组大鼠肝组织MDA含量(nmoL/mg蛋白)分别为0.14±0.01、0.24±0.01、0.36±0.01、0.60±0.01,均显著低于A组的0.27±0.01、0.66±0.01、0.56±0.01、0.93±0.02(P<0.05),在第64周时还明显低于C组的0.84±0.03(P<0.05);B组在第28、42和64周时8-OHdG蛋白的表达强度均显著低于A组(P<0.05).结论 EGb761能够明显抑制AFB_1诱发大鼠肝癌的发生,这可能与其降低了自由基所致的脂质过氧化反应、减轻AFB_1诱导的氧化损伤有关.