目的:探索大小承气汤为基础的多因素大鼠脾虚模型和脾虚肝癌模型的制作方法和成模差别。方法采用苦寒泻下、寒湿环境、劳累、隔天禁食的方法制作脾虚大鼠模型,其中苦寒泻下因素采用大承气汤和小承气汤分别干预;Walker256大鼠肝癌细胞经裸鼠皮下增殖后移植入大鼠肝脏,制作肝癌模型。大鼠随机分为正常组、空白肝癌组、大承气汤组、小承气汤组,每组15只3周龄Wistar雄性大鼠,脾虚因素干预30 d后恢复7d制作肝癌模型并观察35 d。实验过程中观察动物脾虚程度、体重变化、成瘤情况、生存时间等。结果大、小承气汤组动物在脾虚造模过程中相对于对照组(P<0.01),体重增长受到明显抑制,脾虚造模前20 d大承气汤组动物体重均高于小承气汤组(P<0.05),之后二者无差别(P>0.05)。大、小承气汤组动物平均脾虚积分高于空白肝癌组,小承气汤组最高( P<0.01)。肝癌模型总成瘤率91.1%,空白肝癌组为80%,大、小承气汤组均为93.3%。小承气汤组大鼠平均生存天数小于肝癌组和大承气汤组( P<0.01和0.05)。生存分析提示脾虚积分高的肝癌模型和小承气汤组肝癌模型的生存能力明显下降( P<0.05)。结论小承气汤在多因素制作脾虚模型过程中致脾虚作用比大承气汤强,脾虚明显是肝癌模型预后不良的重要因素。
Objective To explore the establishing methods and differences of rat models of spleen deficiency and spleen deficiency liver cancer using the traditional Chinese medicine Dachengqi and Xiaochengqi decoctions .Methods Spleen-deficiency rat models were developed by multifactor methods:bitter-cold purgation ( Dachengqi or Xiaochengqi de-coction), cold-wet environment, tiredness, and fasting on alternate days for 30 days.Seven days after spleen-deficiency modeled,liver cancer in the spleen-deficiency rats and normal rats was developed by subcutaneously inoculation of Walker -256 carcinoma cell line in nude mice and then transplanted into rat livers .Liver cancer models were observed for 35 days. Sixty 3-week old male Wistar rats were randomly distributed into 4 groups: normal group , liver cancer model group , and Dachengqi and Xiaochengqi decoction groups .Degree of spleen deficiency , changes of the body-weight, survival time and tumor formation were recorded .Results Spleen deficiency rat models were successfully established .The weight gain of rats in the spleen-deficiency groups was significantly inhibited (P〈0.01), and during the first 20 days (but not later) the average body weight of the Dachengqi decoction group was significantly higher than that of the Xiaochengqi decoction group (P〈0.05).Spleen-deficiency scores of rats in the Xiaochengqi and Dachengqi groups were higher than those in the blank tumor group, especially in the Xiaochengqi group (P〈0.01).The total tumor formation rate was 91.1%and 80%in the blank tumor groups , and 93.3%in both Xiaochengqi and Dachengqi groups , respectively .The average survival time of Xi-aochengqi group was lower than that of the blank tumor and Dachengqi groups ( P〈0.01 and P〈0.05 ) .The cumulative survival rate of the Xiaochengqi group and rats with a higher spleen-deficiency score was lower than that of the other groups (P〈0.05).Conclusions Xiaochengqi decoction may induce spleen deficiency more seriously than Dache