西番莲酸性多糖改善2型糖尿病糖脂代谢紊乱的机制研究

At present, studies have shown that acid polysaccharides of Passiflora edulis have a significant hypoglycemic effect, inhibition of α-amylase and α-glucosidase activity is one of the main mechanism of action. In the research of this topic, the hypoglycemic activity of acid polysaccharides of Passiflora edulis and the regulation of glucose metabolism in diabetic rats would be systematically studyed, and α-glucosidase inhibitor screening model and hyperglycemic animal model would be used to screen and identify acid polysaccharides. In addition, the chromatographic techniques would be used to prepare full-scale oligosaccharides with different degrees of polymerization and determine the linkage, sequence and branching of oligosaccharides by HPLC-ESI-MS/MS to investigate the inhibitory effect of oligosaccharides on α-glucosidase, and provide more abundant information for structural analysis of polysaccharides. By comparing the structural information of polysaccharide and its oligosaccharide fragments and activity differences, the structural basis and active center of α-glucosidase inhibition of acid polysaccharides of Passiflora edulis would be clarified, studying hypoglycemic mechanism of acid polysaccharides of Passiflora edulis lay the foundation for the development and development of a new α-glycosidase inhibitor drugs provide a scientific basis.

目前已有研究表明西番莲酸性多糖具有显著的降血糖作用，而抑制α-淀粉酶和α-葡萄糖酶活性是其主要的作用机理之一。在本课题的研究中，我们对西番莲酸性多糖及其寡糖片段的降血糖活性和调节糖尿病大鼠的糖脂代谢水平的性质进行系统研究。采用α-糖苷酶抑制剂筛选模型和高血糖动物模型筛选等方法对酸性多糖及其寡糖片段进行筛选和鉴定；采用色谱技术制备不同聚合度的全序列寡糖片段，并利用HPLC-ESI-MS/MS方法测定寡糖的连接、序列及分支，以探讨酸性多糖及其寡糖片段对α-糖苷酶的抑制作用，并为西番莲多糖构效关系解析提供更丰富的信息。通过对酸性多糖及其寡糖片段结构信息的整合及活性差异的比较分析，期望阐明西番莲酸性多糖及其寡糖片段抑制α-糖苷酶的结构基础和活性中心，为深入研究西番莲酸性多糖的降糖机制奠定基础，为研制和开发新的α-糖苷酶抑制剂类药物提供科学依据。

对系列西番莲酸性多糖的降解片段进行结构解析，确定其单糖组成、糖链链接顺序和连接方式、取代集团类型和取代度、异头碳构型、分子折叠特点和分子表面特征等结构特点。解析活性多糖的寡糖片段详细结构，为西番莲酸性多糖结构解析提供更多证据。用建立α-糖苷酶直接作为底物的筛选模型，确定具有α-糖苷酶抑制活性的寡糖片段；通过检测高血糖动物在淀粉负荷后血糖变化来进一步验证多糖对α-糖苷酶抑制作用，最终确定具有α-糖苷酶抑制活性的糖结构。以高脂和 STZ 诱导的 2 型糖尿病大鼠作为研究对象，从肠道菌群-短链脂肪酸-炎症状态-胰岛素抵抗为出发路线，研究寡糖片段对胰岛素抵抗的缓解作用，从而分析其对糖尿病的影响。通过四年的项目研究，研究成果在Fronties in Nutrition, Frontiers in pharmacology, Food Bioscience, Carbohydrate Polymers等国内外高水平学术期刊上发表。