基于UPLC-Q-TOF/MS技术的滋补脾阴法防治糖尿病认知功能障碍的物质基础及代谢通路研究

糖尿病认知功能障碍（diabetic cognitive dysfunction, DCD）是中老年糖尿病患者常见的并发症，我们既往研究工作已证实滋补脾阴法可通过多种机制防治DCD，但其药效物质基础及相关作用代谢通路尚有待深入探讨。申请者前期研究发现DCD患者主要涉及鞘磷脂、尿酸以及苯丙氨酸等代谢通路的紊乱。本研究在此基础上，采用UPLC-QTOF/MS技术整合质谱数据处理的质量丢失滤过（MDF）技术和模式识别系统等方法，探讨DCD大鼠经滋补脾阴法治疗前后，血浆和尿液中内源性代谢成分的差异以及血浆和尿液中的移行成分，推测滋补脾阴法作用的主要代谢通路和真正发挥作用的药效成分；并将代谢通路与药效物质相关联，利用体外细胞分子生物学实验进行验证与深入研究。从而揭示滋补脾阴法防治DCD的物质基础，为方药的开发利用奠定基础；阐明DCD的病因机制及滋补脾阴法的防治机制，为DCD的防治提供有效策略。

Diabetic cognitive dysfunction (DCD) is a common complication in elderly patients with diabetes. It was verified that therapeutic method of tonifying spleen yin could prevent and treat DCD by multiple mechanism in our previous work. However, the material basis and related metabolic pathway need to further discuss. The applicant has found metabolic disorders of sphingophospholipid metabolism, uric acid metabolism and phenylalanine metabolism were existed in DCD patients in previous works. In this study, the integrative technology of UPLC-QTOF/MS, MDF, mother ion extraction and pattern recognition system were applied to investigate the endogenous metabolites discrepancy and the constituents absorbed in plasma and urine before and after treatment with therapeutic method of tonifying spleen yin . Main metabolic pathway and real efficient components were presumed. The effects of efficient components towards metabolic pathway was testified using molecular biology of the cell in vitro. It revealed the material basis for therapeutic method of tonifying spleen yin for treating DCD, and built up a basis for developing this prescription. It also elucidatede the etiological mechanism of DCD and the prevention mechanism of therapeutic method of tonifying spleen yin , and provide effective strategy for DCD treatment.