基于代谢组学探讨芪杉方对肺癌模型小鼠的调控机制

Controlling mechanisms of Qishan Fang based on metabonomics in mouse model of lung cancer

目的研究芪杉方干预肺癌模型小鼠内源性代谢物的变化,探索与肺癌密切相关的代谢物、代谢通路及其芪杉方的治疗作用。方法建立Lewis肺癌模型小鼠,随机分成芪杉方组、模型组和空白组。利用UPLC-HDMS技术平台对各组小鼠血液进行代谢组学分析,Ezionfo软件分析质谱代谢轮廓,通过非监督型主成分分析(OPLS-DA),结合HMDB、KEGG数据库检索和Progenesis QI软件鉴定化合物,分析肺癌相关的潜在代谢生物标记物。进一步研究芪杉方对血液代谢轮廓及生物标志物的影响,探讨芪杉方干预Lewis肺癌模型小鼠血液代谢组学的机制。结果确定22个可能与肺癌相关的代谢生物标记物。发现芪杉方对肺癌相关的18个代谢标记物具有明显的回调作用,进一步将鉴定得到的具有回调作用的标志物进行MetPA分析,得到7个代谢通路,分别是:嘧啶代谢;不饱和脂肪酸的生物合成;硒氨基酸代谢;磷酸戊糖途径;谷胱甘肽代谢;半胱氨酸和蛋氨酸代谢;甘氨酸丝氨酸苏氨酸代谢。结论基于代谢组学的研究方法发现芪杉方通过调节肺癌相关的代谢生物标记物,对肺癌起到了一定的治疗作用。

Objective To study the changes of endogenous metabolites in mouse model of lung cancer after intervention by Qishan Fang(Milkvetch Root and Taxus chinensis Formula),and investigate the metabolites and metabolic pathway related closely to lung cancer,and therapeutic effect of Qishan Fang.Methods The mouse model of Lewis lung cancer was established and all mice were randomly divided into Qishan Fang group,model group and blank group.The blood samples of all groups were given metabonomics analysis by using UPLC-HDMS technology platform.The mass spectrometry metabolic profiling was analyzed by using Ezionfo software.The potential metabolic biomarkers related to lung cancer were analyzed through OPLS-DA combined with retrieving of HMDB and KEGG and Progenesis QI software for compound identification.The influence of Qishan Fang on blood metabolic profiling and biomarkers were further studied,and mechanism of Qishan Fang in intervening blood metabonomics in Lewis mouse model of lung cancer.Results There were 22 metabolic biomarkers may related to lung cancer.It was found that Qishan Fang had significantly callback effect on 18 metabolic biomarkers related to lung cancer.The identified biomarkers with callback effects were further given MetPA analysis and 7 metabolic pathways were obtained,including pyrimidine metabolism,biosynthesis of unsaturated fatty acids,selenoamino acid metabolism,pentose phosphate pathway,glutathione metabolism,cysteine and methionine metabolism,and glycine serine and threonine metabolism.Conclusion It was found that has some therapeutic effects on lung cancer through regulating metabolic biomarkers related to lung cancer based on metabonomics research method.