时正媛 李京峰 宝丽 杨春静 续茜桥 杨璐

摘要 目的：本研究采用超高效液相色谱-串联四极杆飞行时间质谱（UPLC-Q-TOF-MS/MS）技术，探讨了金芪降糖片（JQJT）治疗2型糖尿病（T2DM）的作用机制。方法：采用高糖高脂饮食联合链脲佐菌素（STZ）诱导T2DM模型，检测大鼠体质量、血糖等指标。利用UPLC-Q-TOF-MS/MS分析对照组、模型组、阳性药组、正常给中药组、模型给中药组大鼠的血清样品代谢谱。采用主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）对差异代谢物进行筛选和鉴别。结果：从血清中筛选出15个潜在的生物标志物，并利用Met PA构建了1条相关的代谢通路，即甘油磷脂代谢通路。在2型糖尿病（T2DM）大鼠血清中，溶血磷脂酰胆碱（LysoPC）（18∶0）和LysoPC（16∶1）等9种代谢物下调，LysoPC（18∶1）和LysoPC（20∶0）等6种代谢物上调。结论：金芪降糖片给药组能使这15种潜在的生物标志物有良好的回调趋势，推测金芪降糖片可能通过调节脂代谢紊乱而缓解T2DM的进程。

关键词 金芪降糖片;2型糖尿病;代谢组学;超高效液相色谱串联四极杆飞行时间质谱;血清;中药;甘油磷脂代谢;生物标志物

Serum Metabolomics of Jinqi Jiangtang Tablets in Rats with Type 2 Diabetes Mellitus

SHI Zhengyuan，LI Jingfeng，BAO Li，YANG Chunjing，XU Xiqiao，YANG Lu

（Department of Pharmacy，Beijing Shijitan Hospital，Capital Medical University，Beijing 100038，China）

Abstract Objective：This study aims to explore the mechanism of Jinqi Jiangtang Tablets（JQJT） in the treatment of type 2 diabetes mellitus（T2DM） by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）.Methods：To be specific，T2DM was induced in rats with high-sugar and high-fat diet and streptozotocin（STZ） and the body weight，blood glucose，and other indicators were detected.UPLC-Q-TOF-MS/MS was employed to analyze the metabolic profiles of serum samples in control group，model group，positive drug group，JQJT normal group，and JQJT model group.Principal component analysis（PCA） and orthogonal partial least squares discriminant analysis（OPLS-DA） were used to screen and identify the differential metabolites.Results：Metabolic profiling revealed 15 metabolites as the potential biomarkers distinguishing rats in model group from those in control group.The metabolomics pathway analysis（MetPA） was applied to investigate the underlying metabolic pathways.A major metabolic pathway was glycerophosphatide metabolism.Nine metabolites such as LysoPC（18∶0） and LysoPC（16∶1） were down-regulated in T2DM rats，and six metabolites such as LysoPC（18∶1） and LysoPC（20∶0） were up-regulated.Conclusion：Moreover，the fifteen biomarkers of each administration group had a trend of returning to the levels in rats in control group.The significantly-altered metabolite levels indicated that JQJT can improve the progression of T2DM by alleviating lipid metabolism disorder.

Keywords Jinqi Jiangtang Tablets; Type 2 diabetes mellitus; Metabolomics; UPLC-Q-TOF-MS; Serum; Chinese medicine; Glycerophosphatide metabolism; Biomarker

中圖分类号：R587.1文献标识码：Adoi：10.3969/j.issn.1673-7202.2022.08.00878CC4C84-3415-48A0-AF5B-E9BAD9193C12

2型糖尿病（Type 2 Diabetes Mellitus，T2DM）又称非胰岛素依赖型糖尿病，是一种代谢性疾病，由于胰岛素缺乏导致机体代谢紊乱。目前糖尿病的治疗方法很多，包括合理控制饮食、适度运动、药物治疗等[1-5]。降糖药主要分为中药和西药。虽然中药的降糖速度和疗效不如西药，但中药在预防糖尿病并发症的发生和发展方面有一定的优势。因此，中药治疗糖尿病的机制越来越受到关注和重视[6]。

金芪降糖片（JQJT）源于孙思邈的《千金方》，是由黄连、黄芪、金银花组成的纯中药制剂。……