胸腺肽α1为基础三联抗肿瘤疗法降低肝癌模型大鼠发癌率和血清甲胎蛋白水平

Triplet anti-tumor therapy based on thymosin α-1 attenuates incidence of hepatoma and serum alpha-fetoprotein level in rat hepatoma model

目的探讨以胸腺肽α1(Tα1)为基础,联合槐耳颗粒、西罗莫司的三联抗肿瘤疗法对大鼠肝癌模型血清甲胎蛋白(AFP)水平的影响。方法 90只SD大鼠以随机数字法分为Tα1组、槐耳颗粒组、西罗莫司组、三联组、诱癌组和正常对照组,每组15只。除正常对照组外,其余各组均采用化学诱癌法建立SD大鼠肝癌动物模型,自DEN开始处理后即开始用药,三联组采用0.8 mg/kg Tα1皮下注射,开始每日1次,2周后改为每周2次;0.35 g/kg槐耳颗粒灌胃,3次/日;1 mg/kg西罗莫司灌胃,1次/日。其余各单独用药组的用药剂量同三联组,诱癌组和对照组不予以药物治疗,用药持续到第20周。观察各组大鼠在不同时期的行为表现,并检测各组大鼠6、16、18、20周的血清AFP的水平。结果经诱癌处理的各组大鼠在第16周表现出典型的肝癌症状,并从第10周开始相继死去6只,解剖出各只大鼠肝脏,肉眼观察可见肝脏表面不光滑且有结节。肝脏病理检查证实肝癌模型诱导成功。根据第20周存活大鼠的肝癌发生率,表明三联疗法的大鼠肝癌发生率显著低于其他处理组,存活率显著高于其他处理组。三联疗法显著降低大鼠体内血清AFP水平。结论三联疗法能显著延长患癌大鼠的生存时间、降低发癌率和血清AFP水平。

Objeceve To explore the impact of triple anti-tumor therapy based on thymosin α1 （ Tα1 ） combined with Huaier granule（HG） and sirolimus on the level of serum alpha-fetopretein （AFP） in rat models of liver cancer. Methods Ninety Sprague-Dawley rats were randomly divided into triple anti-tumor therapy group, Tα1 group, HG group, sirolimus group, positive control and blank control groups, with 15 rats in each group. Except the blank control group, the rats in the other groups were induced using diethylnitrosamine （DEN） to establish liver cancer models. After DEN treatment, the triple therapy group underwent 0. 8 mg/kg Tα1 subcutaneous injection （from once a day for two weeks to twice a week since the third week）, 0.35 g/kg HG gavage （three times a day） and 1 mg/kg sirolimus gavage （once a day）. The dose of the rest single drug groups were the same with that of the triple therapy group. The positive control and blank control groups were not treated with the drugs. The treatment lasted 20 weeks. Then, the behavior of the rats were observed at the different time points, and the level of serum AFP in the rats were detected at 6, 16, 18, 20 weeks, respectively. Results The typical symptoms of liver cancer were seen in the DEN-induced rats at ]6 weeks. Since the tenth week, 6 rats died one after another. Pathological section of rat liver tissue suggested that the rat models were established successfully. According to the incidence rate of liver cancer and the survival rate at 20 weeks, the tdple anti-tumor therapy was significantly superior to the single drug treatments, tn addition, the tripte anti-tumor therapy signiJicantty reduced the level o1 serum AFP in the rats.Conclusion The triple anti-tumor therapy can significantly prolong the survival time of rats with liver cancer, decrease the cancer incidence rate and the level of serum AFP.