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目的 探讨健脾理气合剂阻抑AFB1启动小鼠致肝癌的机理。 方法 选择2月龄ICR小鼠50只,随机分成两组:中药组与对照组。每组25只。预先予中药组小鼠灌服健脾理气合剂,每天25g/kg,共15天。16天时,给予AFB11mg/kg,腹腔内注射。用RIA法测定两组小鼠暴露AFB1后0、05、1、2、4、8、24h共7个不同时相肝脏AFB1DNA加成物的含量,并检测与AFB1代谢相关的两相酶系活性。 结果 健脾理气合剂能使小鼠暴露AFB1后高峰时相(1h)的肝脏AFB1DNA加成物水平显著降低(3491±481比4136±282pmol/mgDNA,P<005)。该合剂能诱导小鼠肝脏P450还原酶活性(15107±2889比9593±2642nmol/L细胞色素C/min/mg蛋白,P<001)及GST活性(804±082比595±081μmol/L产物/min/mg蛋白,P<001),并能提高肝脏GSH的含量(10164±0772比8032±0828nmol/g肝组织,P<001)。 结论 健脾理气合剂能通过增强小鼠肝脏Ⅰ相及Ⅱ相解毒酶功能、减少肝脏AFB1DNA加成物形成,而阻抑AFB1启动致肝癌作用。
Objective To investigate the mechanism of Jianpi Liqi Mixture in suppressing liver cancer induced by AFB1 in mice. Methods Fifty 2-month-old ICR mice were randomly divided into two groups: traditional Chinese medicine group and control group. 25 animals per group. The mice of the traditional Chinese medicine group were pre-administered with Jianpi Liqi Mixture, 25g/kg daily for 15 days. At 16 days, AFB 11 mg/kg was given intraperitoneally. The content of AFB1 DNA adducts in liver of 7 groups at 0, 05, 1, 2, 4, 8 and 24 hours after exposure to AFB1 was determined by RIA and the two-phase enzyme activity related to AFB1 metabolism was detected. . RESULTS: Jianpi Liqi Mixture could significantly reduce the level of AFB1 DNA adducts in the liver (1491±481 vs 4136±282 pmol/mg DNA, P<005) after peak exposure (1 h) after exposure to AFB1 in mice. The mixture can induce liver P450 reductase activity (15107±2889 vs 9593±2642 nmol/L cytochrome C/min/mg protein, P<001) and GST activity (804±082=595±081 μmol/L product/min /mg protein, P<001), and can increase the liver GSH content (10164±0772 vs. 8032±0828 nmol/g liver tissue, P<001). Conclusion Jianpi Liqi Mixture can inhibit the activation of AFB1-induced hepatocarcinoma by enhancing the function of liver detoxification enzymes of phase I and II in mice and reducing the formation of hepatic AFB1 DNA adducts.