基于代谢组学研究鹅掌草三萜皂苷抑制肝癌初步作用机制  

Preliminary Study on the Mechanism of Inhibitory Effect of Triterpenoid Saponins of Anemone flaccida on Liver Cancer Based on Metabonomics

作　　者：姚诗琪 莫国艳[1] 韩林涛[1] YAO Shiqi;MO Guoyan;HAN Lintao(Key Laboratory of the Ministry of Education of Hubei University of Chinese Medicine,Wuhan 430065)

机构地区：[1]湖北中医药大学中药资源与中药复方省部共建教育部重点实验室,湖北武汉430065

出　　处：《湖北中医药大学学报》2020年第4期5-9,共5页Journal of Hubei University of Chinese Medicine

基　　金：湖北省教育厅优秀中青年科技创新团队计划项目(项目编号:T201608)。

摘　　要：目的观察通过气相色谱与质谱联用(GC-MS)的代谢组学方法分析鹅掌草三萜皂苷对裸鼠H22肝癌细胞构建的裸鼠皮下移植瘤模型肝癌增殖的影响,为阐明鹅掌草三萜皂苷对肝癌增殖的抑制效应机制,为治疗肝癌提供理论基础。方法建立H22肝癌细胞裸鼠皮下移植瘤模型,实验分为模型组与鹅掌草三萜皂苷高、中、低剂量(15,10,5mg/kg)组,给药干预21d后,绘制肿瘤生长曲线;收集模型组与高剂量组肿瘤组织进行代谢组学分析。结果不同浓度(15,10,5mg/kg)的鹅掌草三萜皂苷干预21d后,与模型组(0mg/kg)比较,均能抑制H22肝癌移植瘤增殖,其中高剂量组抑制肿瘤增殖效果最显著。通过GC-MS分析,共筛选出70种代谢产物为明显改变的代谢产物,其中高剂量组相对模型组下调代谢物有47个。差异代谢物KEGG功能分析表明,代谢物主要与组氨酸代谢、精氨酸和脯氨酸代谢、β-丙氨酸新陈代谢等代谢通路有关。结论鹅掌草三萜皂苷可以有效抑制肝癌移植瘤生长,组氨酸代谢可能在三萜皂苷抑制肝癌细胞增殖中发挥作用。Objective By using the metabolomics method combined with gas chromatography-mass spectrometry(GCMS),the effects of triterpenoid saponins of Anemone flaccida on the proliferation of subcutaneous xenograft hepatoma model of nude mice H22 hepatoma cells were analyzed,so as to elucidate the inhibitory mechanism of triterpenoid saponins of Anemone flaccida on the proliferation of hepatoma and provide a theoretical basis for the treatment of hepatoma.Methods Subcutaneous xenograft models of H22 HCC cells in nude mice were established.The experiments were divided into model group and highdose medium-dose and low-dose(15,10,5 mg/kg) groups.The tumor tissues of model group and high dose group were collected for metabolomics analysis.Results After 21 days of intervention with different concentrations(15,10,5 mg/kg) of triterpenoid saponins of Anemone flaccida,compared with model group(0 mg/kg),both of them could inhibit the proliferation of H22 tumor tissues,among which high-dose group had the most significant effect.Through GC-MS analysis,a total of 70 metabolites were screened as significantly altered metabolites,among which 47 metabolites were down-regulated in high-dose group compared with model group.Functional analysis of KEGG metabolites showed that metabolites were mainly related to histidine metabolism,arginine and proline metabolism,alanine metabolism and other metabolic pathways.Conclusion Triterpenoid saponins of Anemone flaccida can inhibit the growth of liver cancer transplanted tumor effectively,and histidine metabolism may play a role in the inhibitory effect of triterpenoid saponins of Anemone flaccida on the proliferation of liver cancer cells.

关 键 词：肝癌 H22细胞 鹅掌草三萜皂苷 代谢组学 组氨酸代谢 

分 类 号：R285.5[医药卫生—中药学]