不同酸性基团、不同电荷密度、不同分子量植物多糖修复受损伤HK-2细胞能力的构效关系

Renal epithelial cell injury is an important factor to the formation of calcium oxalate nephrolithiasis, while the repair on injured cells will effectively reduce the occurrence rate of kidney stone. This project will comparatively study the structure-activity relationships between 30 kinds of seaweed polysaccharides and Chinese herbal polysaccharides with different chemical structures and their repair ability on injured human renal proximal tubular cells (HK-2), and study the effect of acidic group species, acidity strength (pKa1), charge density and molecular weight of polysaccharides on their repair ability. The acidic functional groups include sulfated group (-OSO3-) and carboxyl group (-COO-); the charge density of polysaccharides are achieved through controlling their acid group content of about 22%, 17%, 13%, 8% and 4%, respectively; the molecular weight of each polysaccharide are about 4000,10000 and 30000 Da. We will study the impact of the chemical structure of polysaccharides on the repair degree and repair order in different subcellular organelles of the injured cells, including cell membrane, mitochondria, cell nucleus, DNA, lysosome and so on, to obtain the concentration- and time-dependent relationships of repair ability in the repairing process of polysaccharides on injured cells. It will provide reference to suppress the formation of kidney stones and to develop original defending-stones polysaccharides drugs. It has not been reported at home and abroad, which is creative and advanced.

肾小管上皮细胞损伤是导致肾结石形成的重要诱因，对损伤细胞进行修复可以降低肾结石发生的几率。本项目比较研究30种具有不同化学结构的海藻多糖和中草药多糖对受损伤人肾近曲小管上皮细胞(HK-2)进行修复的构效关系，探讨多糖中酸性基团种类、电荷密度和分子量对其修复能力的影响。酸性基团包括硫酸基(-OSO3-)和羧基(-COO-)；多糖的电荷密度通过控制其酸性基团含量(在4%~22%之间)实现；每种多糖分子量约4000、10000和30000 Da。重点研究多糖的化学结构对损伤细胞中不同亚细胞器(细胞膜、线粒体、细胞核、DNA、溶酶体等)的修复程度和修复先后顺序，为抑制肾结石形成和开发原创性防石多糖提供启示。

肾小管上皮细胞损伤是导致肾结石形成的重要诱因，对损伤细胞进行修复可以降低肾结石发生的几率。本项目比较研究了38种具有不同化学结构的海藻多糖和中草药多糖对受损伤人肾近曲小管上皮细胞(HK-2)进行修复的构效关系，探讨多糖中酸性基团种类、电荷密度和分子量对其修复能力的影响。酸性基团包括硫酸基(-OSO3-)和羧基(-COO-)；多糖的电荷密度通过控制其酸性基团含量(在5.5%~21.7%之间)实现；每种多糖分子量约2000、4000、10000和30000 Da左右。重点研究了多糖的化学结构对损伤细胞中不同亚细胞器(细胞膜、线粒体、细胞核、DNA、溶酶体等)的修复程度和修复先后顺序，为抑制肾结石形成和开发原创性防石多糖提供启示。.本项目发表论文8篇，其中7篇的影响因子(IF)>3。培养博士后2人，硕士生7人。共参加本领域会议10人次，其中国际会议5人次，全国会议5人次；作会议报告10人次；欧阳健明两次作为组委会成员。在此基础上，博士后孙新园在2017分别获得国家自然科学基金青年科学基金和中国博士后科学基金项目，上述项目均是本项目的延续和深入。