基于UPLC-Q-TOF-MS技术的白花蛇舌草干预结肠炎相关结肠癌小鼠血清代谢组学分析

Serum Metabonomics Analysis of Colitis Associated Cancer Mice Intervened by Hedyotis diffusa Based on UPLC-Q-TOF-MS

目的:研究白花蛇舌草(HDW)对结肠炎相关结肠癌(CAC)模型小鼠的干预作用,并探索其作用机制。方法:采用致癌剂氧化偶氮甲烷(AOM)与致炎剂葡聚糖硫酸钠(DSS)协同作用建立CAC小鼠模型,通过疾病活动指数(DAI),结肠组织形态、病理损伤评分及成瘤率评价HDW对CAC小鼠的干预作用;采用超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS)技术,结合多元统计分析方法,对小鼠血清进行代谢组学分析,探讨HDW干预CAC的作用机制。结果:HDW可以显著改善CAC小鼠一般状况,降低DAI,结肠大体形态和组织病理学评分、成瘤率显著降低。与正常组相比,模型组筛选得到差异代谢物38种,其中包括潜在生物标志物11种,涉及主要代谢通路11条;HDW可显著调节模型组差异代谢产物9种[烟酰胺,尿苷,4-吡哆酸,溶血磷脂酰胆碱(18∶0),溶血磷脂酰乙醇胺(0∶0/20∶0),肌肉肌醇,嘌呤,二氢鞘氨醇-1-磷酸,十四烷二酸],其中包括潜在生物标志物2种(肌肉肌醇、烟酰胺),可调控烟酸盐和烟酰胺代谢、肌醇磷酸盐代谢。结论:HDW对CAC具有治疗作用,其机制可能与调节能量代谢和糖代谢有关。

Objective:To investigate the intervention of Hedyotis diffusa(HDW)on colitis associated cancer(CAC)model mice and explore its mechanism.Method:The CAC mouse model was established by synergistic action of azoxymethane(AOM)and dextran sulfate sodium(DSS).The intervention of HDW on CAC mice was evaluated by disease activity index(DAI),colonic tissue morphology,pathological injury score and tumorigenesis rate.Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and multivariate statistical analysis were used to analyze the metabonomics of mice serum and to explore the mechanism of HDW intervention on CAC.Result:HDW could significantly improve the general condition of CAC mice,decrease DAI,colon gross morphological score,histopathological score and tumorigenesis rate.Compared with the normal group,38 kinds of differential metabolites were screened in the model group,including 11 potential biomarkers,involving 11 main metabolic pathways.HDW could significantly regulate 9 kinds of differential metabolites[niacinamide,uridine,4-pyridoxic acid,LysoPC(18∶0),LysoPE(0∶0/20∶0),myo-inositol,purine,sphinganine 1-phosphate and tetradecanedioic acid]in the model group,including 2 kinds of potential biomarkers(myo-inositol and niacinamide),and HDW could regulate nicotinate and nicotinamide metabolism and inositol phosphate metabolism.Conclusion:HDW has a therapeutic effect on CAC,which may be achieved by regulation of energy metabolism and glucose metabolism.