醋制五味子调控T2DM肝脏糖脂代谢的物质基础和作用机理研究

Type II diabetes mellitus (T2DM) is popular around the world, the most serious metabolic diseases, and the treatment of diabetes and its complications become a heavy financial burden on society, for the prevention and treatment of T2DM imminent. Based on this idea, combined with previous studies and TCM (traditional Chinese medicine) theories, the present study proposed the working hypothesis that "vinegar-prepared Fructus Schisandrae Chinensis may improve the glucolipid metabolic disorders in type II diabetes mellitus on account of the principles that 'drugs with sour taste can work into the liver meridian' and 'sour taste restricts sweet taste'". Based on the hypothesis, the present study set vinegar-prepared Fructus Schisandrae Chinensis as the research subjects and established high fat diet plus STZ-induced diabetic rat models to explore the material basis of the anti- type II diabetes mellitus functions of Fructus Schisandrae Chinensis through employing spectrum-efficiency-related analytical methods to find an effective component spectrum, combined with chemical isolation and identification method on one hand. On the other hand, from biochemical indicators-gene expression-endogenous metabolic biomarkers levels, with gene chips and metabonomics technologies, the present study intended to trace key factors of the impacts of vinegar-prepared Fructus Schisandrae Chinensis on glucolipid metabolism. Besides, the study was designated to analyze the effects of vinegar-prepared Fructus Schisandrae Chinensis to the signal network of glucolipid metabolism regulation and to clarify its hypoglycemic and lipid-regulation mechanism. In general, these studies aim to provide evidence for the prevention and treatment of type II diabetes mellitus with vinegar-prepared Fructus Schisandrae Chinensis. Furthermore, the present study wants to interpret the rationality scientificity of the principle that "sour taste restricts sweet taste" when applied to prevent and type II diabetes mellitus, which may open up new ideas and methods for the prevention and treatment of type II diabetes mellitus with traditional Chinese medicine.

2型糖尿病（T2DM）是全世界流行的最严重的一种代谢性疾病，糖尿病及其并发症的治疗成为社会沉重的经济负担，对于T2DM的防治迫在眉睫。本项目在中医药理论及前期研究基础上提出"醋制五味子可能通过'酸入肝'，'醋制入肝'，'酸克甘'改善T2DM肝脏糖脂代谢紊乱状态"的工作假说。采用高脂饲料加链脲佐菌素诱导的T2DM大鼠模型，以醋制五味子为研究对象，一方面采用谱效学方法，并结合化学分离鉴定技术，探讨五味子抗T2DM物质基础；另一方面，从生化指标-基因表达-内源代谢物三个层面，采用基因芯片和代谢组学方法，追踪醋制五味子影响2型糖尿病糖脂代谢的关键因子，分析醋制五味子对T2DM肝脏糖脂代谢信号网络的调控，阐明醋制五味子降糖调脂的作用机理。本项目的开展为醋制五味子防治T2DM提供依据；诠释 "酸克甘"防治T2DM的科学内涵，为中医药防治T2DM开辟新思路和新方法。

2型糖尿病（T2DM）是全世界流行的最严重的一种代谢性疾病，糖尿病及其并发症的治疗成为社会沉重的经济负担，对于T2DM的防治迫在眉睫。本项目在提出“五味子可能通过‘酸入肝’，‘酸克甘’改善T2DM糖脂代谢紊乱状态”的工作假说的基础上，采用化学成分群分析-体外活性评价-整体动物药效评价相结合的方法，以高脂饲料加链脲佐菌素联合致糖尿病为动物模型，比较五味子和南五味子抗T2DM肝脏糖脂代谢的差异，研究结果表明南五味子通过调节机体氧化还原平衡，增加肝糖原合成，改善胰岛和肝脏功能等方面调控T2DM肝脏糖脂代谢药效表达明显；在比较五味子和南五味子抗T2DM药效研究基础上，采用高脂饲料加链脲佐菌素联合诱导的糖尿病动物模型，以南五味子、醋制南五味子、醋制南五味子各化学部位为研究对象，以血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、胰岛素，谷胱甘肽，总抗氧化能力等为指标，并结合肝脏胰脏病理切片变化，依次开展其调控T2DM肝脏糖脂代谢研究，最终筛选醋制南五味子石油醚部位和氯仿部位通过调节机体氧化还原平衡，改善脂代谢紊乱状态，降低血糖等方面较为明显的调控T2DM肝脏糖脂代谢；在有效部位筛选基础上，首先以醋制南五味子石油醚部位为研究对象，采用血清药物化学的研究技术和方法分析寻找有效组分群，研究发现外源性化学成分主要滞留在血液和肝脏，其他脏器分布相对较少，这也验证南五味子归肝经及“醋制入肝”的药性理论，后续将结合HPLC/MS的分析手段确认鉴定血清及肝脏组织醋制南五味子石油醚部位和氯仿部位原型化学成分及移行化学成分结构，从而初步阐明南五味子抗糖尿病物质基础。本项目的开展和完成，初步探讨了南五味子防治T2DM的有效性和物质基础，为进一步研究南五味子抗T2DM有效性和作用机理提供依据；也揭示了中医药五味相生相克的“酸克甘”合理性，为进一步阐明“酸克甘”法防治T2DM科学内涵提供参考。