中国中药杂志

2020, v.45(03) 636-644

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基于UHPLC-Q-TOF-MS的当归补血汤治疗2型糖尿病小鼠的代谢组学研究
Metabolomics study of Danggui Buxue Tang on treatment of type 2 diabetes mice using UHPLC-Q-TOF-MS

孙丽丽;白海英;郑文惠;王丽瑶;赵伟;李建银;史彦斌;杨志刚;
SUN Li-li;BAI Hai-ying;ZHENG Wen-hui;WANG Li-yao;ZHAO Wei;LI Jian-yin;SHI Yan-bin;YANG Zhi-gang;School of Pharmacy, Lanzhou University;

摘要(Abstract):

该文运用超高效液相色谱串联四极杆飞行时间质谱(UHPLC-Q-TOF-MS)技术探究当归补血汤(DBT)治疗2型糖尿病(T2DM)的作用机制,采用高糖高脂饲料联合链脲佐菌素(STZ)诱导T2DM模型,检测小鼠体质量、血糖、IL-6和INS等生化指标。利用UHPLC-Q-TOF-MS技术对对照组和模型组小鼠的血清样品进行代谢轮廓分析,结合主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)等多元统计分析方法,筛选差异代谢物并进行鉴别。在血清中筛选出16种潜在的生物标志物,借助MetPA构建了13条相关的代谢通路,筛选出7条主要的代谢途径,分别是缬氨酸、亮氨酸和异亮氨酸的生物合成,甘油磷脂代谢,原发性胆汁酸生物合成,牛磺酸和亚牛磺酸代谢,苯丙氨酸代谢,脂肪酸代谢和不饱和脂肪酸的生物合成。T2DM小鼠血清中甘氨胆酸、牛磺胆酸和棕榈酸等11个代谢物下调,亮氨酸、白三烯E4等5个代谢物上调,各给药组均能使这16种潜在的生物标志物有良好的回调趋势,推测DBT可通过提高机体对胰岛素敏感性、调节糖脂代谢紊乱、减轻炎症反应等缓解T2DM的进程。
In this paper, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS)-based metabolomics approach was used to explore the mechanism of Danggui Buxue Tang(DBT) in treating type 2 diabetes mellitus(T2 DM). T2 DM mice model was induced by high-sugar and high-fat fodder and streptozotocin(STZ). The routine indexes such as body weight, blood glucose, plasma insulin, IL-6 and related organ indexes were determined. The UHPLC-Q-TOF-MS technique was used to analyze the metabolism profile of serum samples between the control group and model group, and multiple statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to screen and identify biomarkers. Metabolic profiling revealed 16 metabolites as the most potential biomarkers distinguishing mice in model group from those in control group. The metabolomics pathway analysis(MetPA) was used to investigate the underlying metabolic pathways. Seven major metabolic pathways such the valine, leucine and isoleucine biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, fatty acid metabolism and biosynthesis of unsaturated fatty acid. Eleven metabolites such as taurocholic acid and palmitic acid were down-regulated in T2 DM mice, and five metabolites such as L-leucine and leukotriene E4 were up-regulated. Moreover, the sixteen biomar-kers of each administration group had a trend of returning to mice in control group. The significantly-altered metabolite levels indicated that DBT can improve the progression of type 2 diabetes by increasing insulin sensitivity, regulating sugar and lipid metabolism disorders, and relieving inflammation.

关键词(KeyWords): 当归补血汤;2型糖尿病;代谢组学;UHPLC-Q-TOF-MS
Danggui Buxue Tang;type 2 diabetes;metabolomics;UHPLC-Q-TOF-MS

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划政府间国际科技创新合作重点专项(2016YFE0129000);; 甘肃省中医药管理局科研课题(GZK-2015-21);; 兰州大学中央高校基本科研业务费专项(lzujbky-2017-k26)

作者(Author): 孙丽丽;白海英;郑文惠;王丽瑶;赵伟;李建银;史彦斌;杨志刚;
SUN Li-li;BAI Hai-ying;ZHENG Wen-hui;WANG Li-yao;ZHAO Wei;LI Jian-yin;SHI Yan-bin;YANG Zhi-gang;School of Pharmacy, Lanzhou University;

Email:

DOI: 10.19540/j.cnki.cjcmm.20191105.202

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