基于UHPLC-QE-MS技术的两色金鸡菊总黄酮干预肺癌移植瘤小鼠瘤组织的代谢组学研究  

Study of total flavonoids from Coreopsis tinctoria Nutt.on tissue metabolomics in xenograft nude mice based on UHPLC-QE-MS

作　　者：国鲁源 阿不来提·阿合买提[2] 布威阿丽耶·胡加阿布都拉 岳进巧[3] 吴桂霞[1] GUO Lu-yuan;ABULAITIA-he-mai-ti;BUWEIALIYE·Hu-jia-a-bu-du-la;YUE Jin-qiao;WU Gui-xia(Department of Physiology,School of Basic Medical Science,Xinjiang Medical University,Urumqi83001l,Xinjiang Uygur Autonomous Region,China;The Functional Center,School of Basic MedicalScience,Xinjiang Medical University,Urumqi 83001l,Xinjiang UygurAutonomous Region,China;Departmentot f Medical Examination,Changji Vocationaalnd Technical College,Changji 831100,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学基础医学院生理教研室,新疆乌鲁木齐830011 [2]新疆医科大学基础医学院机能中心,新疆乌鲁木齐830011 [3]新疆昌吉职业技术学院医学分院生物微生物教研室,新疆昌吉831100

出　　处：《中国临床药理学杂志》2023年第9期1321-1325,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科学基金(2022D01A41,2019D01C218)。

摘　　要：目的利用超高效液相色谱-质谱联用(UHPLC-QE-MS)技术,分析两色金鸡菊总黄酮(CTFs)对非小细胞肺癌移植瘤裸鼠瘤组织中代谢物的影响,初步探讨其抗瘤作用的潜在机制。方法建立非小细胞肺癌移植瘤裸鼠模型。CTFs干预组(100 mg·kg^(-1))从小鼠接种肿瘤细胞起灌胃给药;CTFs治疗组(100 mg·kg^(-1))从移植瘤体积达40~50 mm^(3)后开始灌胃给药,模型组给予等量的羧甲基纤维素钠盐溶液,每天1次,连续21 d,记录瘤质量和体积,并进行苏木精-伊红染色。用UHPLC-QE-MS技术对3组瘤组织进行代谢组分析,用主成分分析法(PCA)和正交偏最小二乘判别分析法(OPLS-DA)筛选出相关差异代谢物,通过KEGG、HMDB数据库进行潜在的代谢通路分析。结果模型组、CTFs干预组和CTFs治疗组瘤质量分别为(0.60±0.15)、(0.21±0.14)、(0.52±0.23)g,瘤体积分别为(453.89±72.38)、(306.71±70.35)、(422.20±77.55)mm^(3),与模型组相比,CTFs干预组中瘤质量及瘤体积明显降低,而CTFs治疗组差异无统计学意义。UHPLC-QE-MS的结果显示,与模型组小鼠相比,CTFs干预组共有43个差异代谢物,涉及15条代谢通路;CTFs治疗组有23个差异代谢物,涉及5条代谢通路。结论CTFs可能通过调节牛磺酸和亚牛磺酸代谢、苯丙氨酸代谢等通路,调控相关代谢产物水平,进而发挥抗肺癌的作用。Objective Theultra-high performance liquid chromatography-mass spectrometry(UHPLC-QE-MS)was used to detect the effects of total flavonoids from Coreopsis tinctoria Nutt.(CTFs)on tissue metabolites in non-small cell lung cancer(NSCLC)tumor-bearing nude mice,to explore the underlying mechanism of the anti-tumor effects of CTFs.Methods Nude mice xenograft model of NSCLC was established.The CTFs intervention group(100 mg·kg^(-1))was administered by gavage from the first day of the inoculation of the tumor cells,the CTFs treatment group(100 mg·kg^(-1))was administered from the transplanted tumor volume of 40 to 50 mm.Model group was given the equal volume of carboxymethyl cellulose sodium salt,once a day for 21 consecutive days,then tumor volume and weight were recorded and calculated,hemotoxylin and eosin staininggwasperformed.The metabolome analysis of the three groups was performed by UHPLC-QE-MS technique,and related differential metabolites were selected by principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA),and potential metabolic pathway analysis was conducted by KEGG and HMDB databases.Results The tumor mass of model group,CTFs intervention group and CTFs treatment group were(0.60±0.15),(0.21±0.14),(0.52±0.23)g,tumor volume were(453.89±72.38),(306.71±70.35),(422.20±77.55)mm^(2),respectively.Compared with model group,the tumor mass and tumor volume in the CTFs intervention group were significantly decreased,while the difference was not statistically significant in CTFs treatment group.The results of UHPLC-QE-MS showed that there were 43 differential metabolites which were mainly enriched in 15 metabolic pathways between CTFs intervention group and model group.Compared with model group,23 differential metabolites were identified in the CTFs treatment group and 5 metabolic pathways were obtained.Conclusion It is speculated that anti-lung cancer effects of CTFs may be related to the regulation of taurine/hypotaurine metabolism,phenylalanine metabolism and ot

关 键 词：两色金鸡菊 肺癌 凋亡 代谢组学 

分 类 号：R28[医药卫生—中药学]