山豆根生物碱对DEN诱发肝癌大鼠的作用及机制研究

Study on the Efficacy and Mechanism of Liver Cancer Induced by DEN in Rats of Alkaloids of Sophorae Tonkinensis Radix Et Rhizoma

关键词:  山豆根  抗肝癌  二乙基亚硝胺  AFP  作用机制  RT-PCR

Key words:  Sophorae Tonkinensis Radix et Rhizoma  anti-liver cancer  diethylnitrosamine(DEN)  AFP  mechanism  RT-PCR

摘要:

目的 在山豆根生物碱成分明确的基础上，开展体内药理药效及作用机制研究。方法 采用DEN诱发肝癌模型，将SD大鼠随机分为空白组，模型组，环磷酰胺组（0.01 g·kg^-1）和山豆根生物碱低、中、高剂量组（0.036，0.108，0.324 g·kg^-1），造模第7周后治疗组给予相应药物，连续给药9周；观察各组大鼠的生理指标及病理组织切片，检测大鼠血清中甲胎蛋白的含量，RT-PCR技术检测肿瘤组织中VEGF、PI3K、PTEN基因表达。结果 与模型组相比，山豆根生物碱低剂量和中剂量组能显著降低大鼠血清中AFP的含量（P<0.05），减少肿瘤组织中癌结节数，同时，山豆根生物碱能不同程度地减少肝组织中VEGF、PI3K mRNA表达，增加PTEN mRNA表达。结论 山豆根生物碱能产生明确的体内抗肝肿瘤药理作用，改善免疫调节，延长生存时间；其作用机制与环磷酰胺类似，参与VEGF、PI3K及PTEN基因的调控，为山豆根的临床应用提供参考依据。

Abstract:

OBJECTIVE To carry out the pharmacological efficacy in vivo and mechanism research based on clear component of alkaloids of Sophorae Tonkinensis Radix et Rhizoma. METHODS Hepatocarcinoma model rats were induced by diethylnitrosamine (DEN), SD rats were randomly divided into six groups:normal control group, hepatocarcinoma model group, cyclophosphamide group (0.01 g·kg^-1)and low, medium, high dose group of alkaloids (0.036, 0.108, 0.324 g·kg^-1), and seven weeks later treated with corresponding drugs for nine weeks. Observe physiological indexes and pathologic section of each group, the levels of AFP in serum were measured and the expression levels of VEGF、PI3K、PTEN mRNA were analyzed by RT-PCR. RESULTS Compared with model group, the alkaloids of Sophorae Tonkinensis Radix et rhizoma could significantly reduce the content of AFP in serum(P<0.05), Histological examination demonstrated that the number of liver cancer nodes in alkaloids groups were lower than that of model group, at the same time, the alkaloids of Sophorae Tonkinensis Radix et rhizoma could down-regulate the expression of VEGF, PI3K mRNA and up-regulate the expression of PTEN mRNA in liver tissue. CONCLUSION The clear pharmacological effects of liver cancer-suppression in vivo is produced by the alkaloids of Sophorae Tonkinensis Radix et rhizoma. Improved immunity and extended lifetime; Its mechanism is similar with cyclophosphamide, regulation VEGF, PI3K, PTEN expression. Provide a reference basis for alkaloids of Sophorae Tonkinensis Radix et rhizoma for the clinical application.