锁阳多糖及其含硒衍生物的结构和降血糖作用研究

Cynomorium songaricum Rupr. was widely distributed in western China. In our previous study, Cynomorium songaricum polysaccharide (CSP) was a heteropolysaccharide consisting of Ara, Glu and Gal. It could be considered as a potential candidate for developing a new anti-diabetic agent. Most reports had studied the synthesis of Se-polysaccharides with low Se contents. In this project, specific glycosidase methods were employed for structure characterization (monosaccharide composition, linkage of glycosidic bond and branch point) of CSP. Se-polysaccharides with high Se contents were synthesized. The existing form, valence and valence were characterized. The relationship between primary structure and solution conformation was also studied. The safe dose of CSP and Se-CSP was studied in acute toxicity test. Furthermore, hypoglycaemic effects of CSP and Se-CSP were evaluated in vitro and vivo for a better understanding of the relationship between structure and biological response effects. This study could provide evidence for design and synthesis of carbohydrate-modified drugs.

西北地区特产锁阳资源丰富，有待深度研发。项目组前期研究表明锁阳多糖（CSP）是由D-葡萄糖、半乳糖、L-阿拉伯糖3种单糖组成，具有调节血糖功能，有望开发出新的降血糖天然药物。针对CSP缺乏系统、深入的结构研究，硒多糖合成过程中硒含量低等问题，本项目在前期研究的基础上，利用特异性糖苷酶酶解技术结合现代仪器分析手段，系统研究CSP的化学结构（单糖的连接顺序、糖苷键的类型、糖链分支点等）；合成高硒含量的Se-CSP，表征硒含量及其存在形式、价态、取代位置等；研究修饰前后糖链结构的变化对溶液构象及其转变方式的影响。通过体内急性毒性实验确定CSP和Se-CSP的安全剂量；建立体外胰岛素抵抗细胞模型并培养大鼠胰岛瘤细胞INS-1、实验性糖尿病及肥胖大鼠模型，比较研究CSP和Se-CSP的降低血糖效应，阐明CSP和Se-CSP的降血糖作用机理，为开发新的降血糖天然药物提供科学依据。

西北地区特产锁阳资源有待深度研发。项目组前期研究表明锁阳多糖（CSP）是由D-葡萄糖、半乳糖、L-阿拉伯糖3 种单糖组成，具有调节血糖功能，有望开发出新的降血糖天然药物。针对CSP 缺乏系统、深入的结构研究，硒多糖合成过程中硒含量低等问题，本项目在前期研究的基础上，利用现代仪器分析手段，系统研究CSP 的化学结构（单糖的连接顺序、糖苷键的类型、糖链分支点等）；合成高硒含量的Se-CSP，表征硒含量及其存在形式、价态、取代位置等；建立体外胰岛素抵抗细胞模型并培养实验性糖尿病及肥胖大鼠模型，研究CSP的降血糖效应，阐明其降血糖作用机理，为开发新的降血糖天然药物提供科学依据。