高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (6): 1050-1058.doi: 10.7503/cjcu20160035

• 研究论文: 无机化学 • 上一篇    下一篇

肾上皮细胞损伤使草酸钙晶体黏附增强的分子机制

甘琼枝, 孙新园, 姚秀琼, 欧阳健明()   

  1. 暨南大学生物矿化与结石病防治研究所, 广州 510632
  • 收稿日期:2016-01-15 出版日期:2016-06-10 发布日期:2016-05-26
  • 作者简介:联系人简介: 欧阳健明, 男, 博士, 教授, 主要从事生物矿化和纳米材料研究. E-mail:toyjm@jnu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 21371077)资助

Molecular Mechanism of Adhesion of Monohydrate and Dihydrate Calcium Oxalate Crystals on Injured Kidney Epithelial Cells

GAN Qiongzhi, SUN Xinyuan, YAO Xiuqiong, OUYANG Jianming*()   

  1. Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632, China
  • Received:2016-01-15 Online:2016-06-10 Published:2016-05-26
  • Contact: OUYANG Jianming E-mail:toyjm@jnu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.21371077)

摘要:

研究了非洲绿猴肾上皮细胞(Vero)在损伤前后与一水合草酸钙(COM)和二水合草酸钙(COD)晶体的黏附作用及其引起的细胞反应, 探讨了肾结石形成机理. COM和COD晶体与损伤细胞的黏附加重了细胞的过氧化损伤程度, 导致损伤细胞的活力进一步降低, 乳酸脱氢酶(LDH)释放量和活性氧(ROS)进一步增加, 坏死细胞数量进一步增多, 细胞体积缩小, 并出现凋亡小体. COM晶体对细胞的损伤能力显著大于COD晶体. 扫描电子显微镜(SEM)观测结果表明, 损伤组Vero与COM微晶的黏附作用显著强于对照组, 且能促进COM微晶的聚集. 共聚焦显微镜观测结果表明, Vero损伤后, 其表面表达的晶体黏附分子透明质酸(HA)显著增加, HA分子是促进微晶黏附的重要原因. 细胞表面草酸钙的黏附量和晶体聚集程度与细胞的损伤程度成正相关. 本文结果从分子和细胞水平上提示, 细胞损伤是导致草酸钙肾结石形成的重要因素.

关键词: 细胞调控, 生物矿化, 晶体黏附, 草酸钙, 透明质酸

Abstract:

Effects of cell injury on calcium oxalate monohydrate(COM) and calcium oxalate dihydrate(COD) microcrystalline adhesion and cellular response of calcium oxalate microcrystalline on African green monkey renal epithelial(Vero) cells after adhesion were evaluated. COM amd COD crystal adhesion to injured Vero cells increased oxidative damage degree, the LDH release amount, reactive oxygen species(ROS) and dead cells and decreased cell viability. The cells shrinked and apoptotic bodies appeared. COM crystals caused more serious damage to injured Vero cells than COD crystals. The results of scanning electron microscopy(SEM) showed that the adhesive capacity of injured Vero cells to COM was significantly stronger than the control group, which enhanced crystals adhesion and aggregation. Laser scanning confocal microscope showed that Vero cell injury increased the expression of crystal binding hyaluronic acid(HA) molecules which were the most important reasons for promoting microcrystalline adhesion. The microcrystalline adhesion and aggregation on cellular surface were positively correlated to cell injury degree. These findings indicated that cell injury was the leading risk factor of kidney stone formation, which may provide insights into the mechanisms of kidney stone formation from molecular and cellular levels.

Key words: Cell-mediation, Biomineralization, Crystal adhesion, Calcium oxalate, Hyaluronic acid

中图分类号: