不同尺寸、不同晶相、不同形貌草酸钙晶体与肾上皮细胞粘附的比较

Kidney stone is the product of pathologic biomineralization, and calcium oxalate (CaOx) is its main mineral. The adhesion of CaOx crystals in urine on renal tubular epithelial cell (REC) plays a key role in the forming of kidney stone. However, its mechanisms have not been yet clearly clarified so far. On the basis of the previous work we synthesize 11 kinds of CaOx crystals with different sizes, different crystalline phases and different morphologies in this project, namely, the calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals respectively with sizes about 100 nm, 500 nm, 2 μm and 10 μm as well as COM crystals of the spherical, hexagonal and aggregated morphologies. Then we compare the differences of their injuries on normal REC cells and the adhesion on the injured cell surfaces so as to explore the size effect, time effect and dose effect on the interaction process between different properties of CaOx crystals and REC cells. Especially, we want to compare the differences in the interaction processes of crystals with REC cells, that is, the difference between nano- CaOx crystals and micro- CaOx crystals, the difference between COM crystals and COD crystals and the difference among COM crystals of the spherical, hexagonal, and aggregated morphologies. This project also investigates the ability differences of inhibiting the adhesion of CaOx crystals and internalizing CaOx crystals after the injuried REC cells were repaired. The chemical models about the adhesion of CaOx crystals with different sizes, different crystalline phases, different morphologies on the injuried cells will be established. The molecular mechanisms about cell damage, crystal adhesion, cell endocytosis and cell repair with kidney stone formation will be elaborated from the perspective of hydrogenbonds, electrostatic interactions, spatial matching and weak interaction force etc.cellular and molecular levels, so as to provide a new enlightenment for clinical inhibition of the kidney stone formation.

肾结石是病理生物矿化的产物，其主要矿物为草酸钙(CaOx)。肾小管上皮细胞(REC)与尿液中CaOx晶体的粘附在肾结石形成过程中起着关键作用，但其分子机理仍未阐明。本项目在前期工作的基础上，制备11种不同尺寸、不同晶相、不同形貌的CaOx晶体，即粒径分别约100 nm、500 nm、2 μm、10 μm的一水草酸钙(COM)和二水草酸钙(COD)晶体及球形、六边形、聚集状COM晶体；研究它们对正常REC细胞的损伤能力及其与损伤细胞的粘附能力差异；探讨不同性质CaOx晶体与细胞作用时的尺寸效应、时间效应和剂量效应；特别是纳米晶体与微米晶体、COM与COD、不同形貌晶体与细胞作用的差异；研究损伤细胞在修复前后抑制晶体粘附和内吞晶体能力的差异。从氢键、静电作用、空间匹配和弱相互作用力等方面阐述细胞损伤、晶体粘附、细胞内吞与肾结石形成的细胞和分子机制，为临床上抑制肾结石形成提供新的启示。

肾结石是病理生物矿化的产物，其主要矿物为草酸钙(CaOx)。肾小管上皮细胞(REC)与尿液中CaOx晶体的粘附在肾结石形成过程中起着关键作用，但其分子机理仍未阐明。本项目制备了26种不同尺寸、不同晶相、不同形貌的CaOx晶体，即粒径分别约50 nm、100 nm、200 nm、600 nm、1 μm、3 μm、10 μm和20 μm的一水草酸钙(COM)和二水草酸钙(COD)晶体及5个不同形貌的COM晶体和5个不同形貌的COD晶体。研究了它们对正常REC细胞的损伤能力及其与损伤细胞的粘附能力差异；探讨了不同性质CaOx晶体与细胞作用时的尺寸效应、时间效应和剂量效应；特别是纳米晶体与微米晶体、COM与COD、不同形貌晶体与细胞作用的差异；研究了损伤细胞在修复前后抑制晶体粘附和内吞晶体能力的差异。从氢键、静电作用、空间匹配和弱相互作用力等方面阐述细胞损伤、晶体粘附、细胞内吞与肾结石形成的细胞和分子机制，为临床上抑制肾结石形成提供新的启示。.本项目发表论文20篇，其中10篇的IF>4，5篇的IF>3。共参加本领域会议11人次，其中国际会议8人次，全国会议3人次；作会议报告2人次；2次为组委会成员。培养博士生1人，硕士生9人。共有3名研究生获得了研究生国家奖学金。在此基础上，本人欧阳健明及博士生孙新园分别在2017、2018年获得后续国家基金。