罗昌国+张晶+李阳

[摘要] 目的 觀察四君子合小柴胡汤对移植性原发性肝癌小鼠肿瘤生长的影响。方法 100只肝郁脾虚型移植性原发性肝癌小鼠随机分为模型组、5-FU 组、四君子汤组（简称四君组）、小柴胡汤组（简称柴胡组）、四君子合小柴胡汤组（简称君柴组），每组20只。模型组、四君组、柴胡组、君柴组小鼠分别给予蒸馏水、四君子汤、小柴胡汤、四君子合小柴胡汤灌胃，每天1次，连续给药10d；5-FU 组隔天1次给予 5-FU注射液腹腔注射，给药5次。观察各组小鼠的体质量、瘤重、肿瘤细胞凋亡、细胞周期。结果 小鼠体质量比较，各组显著高于模型组（P<0.05），君柴组高于5-Fu组（P<0.05）。比较小鼠去瘤体质量，各组显著高于模型组（P<0.05），君柴组高于5-Fu组（P<0.05）。比较肿瘤瘤重和抑瘤指数，5-Fu组、君柴组显著低于模型组、四君组和柴胡组，差异有统计学意义（P<0.05）。比较抑瘤率，5-FU 组、君柴组显著高于四君组和柴胡组（P<0.05）。细胞凋亡比较，君柴组高于四君组、柴胡组（P<0.05），显著高于模型组（P<0.01）。比较肿瘤细胞凋亡，其余4组均显著高于模型组（P<0.05），君柴组显著高于四君组和柴胡组（P<0.05）；细胞周期所占百分比比较，5-Fu组、君柴组G0-G1期细胞显著高于模型组（P<0.05）；S期细胞百分比，5-Fu组、君柴组G0-G1期细胞显著低于模型组、四君组和柴胡组（P<0.05），G2-M 期各组比较差异无统计学意义（P>0.05）。结论 四君子合小柴胡汤对肝郁脾虚型移植性原发性肝癌小鼠有抑瘤作用，比四君子汤、小柴胡汤单独应用好，其作用机制主要是诱导肝癌细胞凋亡。

[关键词] 四君子汤；小柴胡汤；原发性肝癌；动物实验

[中图分类号] R735.7 [文献标识码] A [文章编号] 2095-0616（2017）06-19-04

[Abstract] Objective To observe the effect of Sijunzi decoction combined with Minor Bupleurum decoction on tumor growth of mice with transplanted primary liver cancer. Methods 100 mice of hepatic stagnation and spleen deficiency type with transplanted primary liver cancer were randomly divided into the model group， 5-FU group， Sijunzi decoction group （abbreviated as Sijun group）， Minor Bupleurum decoction group （abbreviated as bupleurum group） and the Sijunzi combined with Minor Bupleurum decoction group （abbreviated as Jun bupleurum group）， with 20 in each. Mice in the model group， Sijun group， bupleurum group and Jun bupleurum group were respectively given gastric perfusion of distilled water， Sijunzi decoction， Minor Bupleurum decoction and Sijunzi decoction combined with Minor Bupleurum decoction for once every day with successive administration for 10 days. 5-FU group was given 5-FU injection by intraperitoneal injection for 5 times for once every two days. Body mass， tumor weight， tumor cell apoptosis and cell cycle of mice in every group were observed. Results Body mass of mice of every group was significantly higher than that of the model group （P<0.05）. Body mass of mice of the Jun bupleurum group was higher than that of the 5-Fu group （P<0.05）. By comparing body mass without tumor weight， that of every group was significantly higher than that of the model group （P<0.05）. Jun bupleurum group was higher than that of the 5-Fu group （P<0.05）. Tumor weight and anti-tumor indexes of the 5-Fu group and Jun bupleurum group were significantly lower than those of the model group， Sijun group and bupleurum group. Differences had statistical significance （P<0.05）. Anti-tumor rates of the 5-Fu group and Jun bupleurum group were significantly lower than those of Sijun group and bupleurum group （P<0.05）. Cell apoptosis of Jun bupleurum group was higher than that of the Sijun group and bupleurum group （P<0.05） and significantly higher than that of the model group （P<0.01）. Tumor cell apoptosis of other four groups was significantly higher than that of the model group （P<0.05）. Tumor cell apoptosis of Jun bupleurum group was significantly higher than that of Sijun group and bupleurum group （P<0.05）. By comparing percentage of cell cycle， G0-G1 stage cells of 5-FU group and Jun bupleurum group were significantly higher than that of the model group （P<0.05）. Percentage of S stage cell， G0-G1 stage cell of 5-FU group and Jun bupleurum group was significantly lower than that of the model group， Sijun group and bupleurum group （P<0.05）. Comparing G2-M stage cells， there were no statistical difference （P>0.05）. Conclusion Sijunzi decoction combined with Minor Bupleurum decoction has anti-tumor effect on mice of hepatic stagnation and spleen deficiency type with transplanted primary liver cancer and it has a better effect than single application of Sijunzi decoction and Minor Bupleurum decoction. The action mechanism is mainly to induce apoptosis of hepatoma cells.

[Key words] Sijunzi decoction； Minor Bupleurum decoction； Primary liver cancer； Animal experiment

原发性肝癌（HCC）是我国常见恶性肿瘤，每年新发肝癌和死于肝癌的患者居全球首位。中医药是我国治疗肝癌的重要方法，通过多年临床实践和研究，中医肝癌诊治已有一些初步共识。肝郁脾虚被认为是原发性肝癌中医证型之一[1]，疏肝健脾法被认为可以用于治疗肝癌，大量临床和实验研究表明四君子汤和小柴胡汤对原发性肝癌有一定的抑瘤和抗转移作用，体外试验表明，四君子汤可通过激活外周血单核细胞发挥抗肿瘤作用[2-3]，小柴胡汤能够抑制癌细胞生长，并诱导肿瘤细胞凋亡[4-5]，四君子汤可健脾，小柴胡汤能疏肝，两方均对原发性肝癌有一定治疗作用，但根据中医理论，两方联合使用才能完整体现“疏肝健脾”的治疗内涵，但两方联合使用的研究尚不多见。……