健脾理气合剂阻抑黄曲霉毒素B_1启动小鼠致肝癌机理

INHIBITION OF JIANPILIQI MIXTURE (JPLQ) ON INITIATING HEPATOCARCINOGENESIS OF AFLATOXIN B 1 IN MICE

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。

PURPOSE To elucidate the inhibition of JPLQ on initiating hepatocarcinogenesis of aflatoxin B 1 (AFB 1) in mice.METHODS Fifty of 2 month old ICR mice were randomly broken into two groups: herb group and control group. Each group included 25 mice. The mice in herb group were orally given 2.5 g/kg body wt/d of JPLQ for 15 days and the control group of mice were only given same volume of saline. At the 16 th day,the two groups of mice were intraperitoneally exposed to single dose of 1 mg/kg body wt of AFB 1. With a competitive radioimmunoassay,seven different time points of hepatic AFB 1 DNA adducts were detected in mice.Two phases of enzyme activities relating to the metobolism of AFB 1 also were examined.RESULTS JPLQ could decrease the mouse hepatic AFB 1 DNA adducts significantly at 1h time point (349.1±48.1 vs 413.6 ±28 2 pmol/mg DNA, P &lt;0 01).Statistically,it could enhance the activities of both P 450 reductase(15.107±2.889 vs 9.593±2.642, P &lt;0 01)and glutathion S transferase(8.04±0.82 vs 5.95±0.81, P &lt;0 01).JPLQ also increased the ammount of hepatic glutathion(10.164±0.772 vs 8.032±0.828, P &lt;0.01) in mice.CONCLUSION Inhibition of JPLQ on initiating hepatocarcinogenesis of AFB 1 might contribute to its decreasing the hepatic AFB 1 DNA adducts in mice by inducing two phases of detoxificating enzymes relating to the metabolism of AFB 1