Size-Dependent Cytotoxicity of Hydroxyapatite Crystals on Renal Epithelial Cells
Size-Dependent Cytotoxicity of Hydroxyapatite Crystals on Renal Epithelial Cells
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DOI：
10.2147/ijn.s232926
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发表时间：
2020-07
影响因子：
8
通讯作者：
Xin-Yuan Sun;Jia-Yun Chen;C. Rao;J. Ouyang
中科院分区：
文献类型：
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作者：
Xin-Yuan Sun;Jia-Yun Chen;C. Rao;J. Ouyang
背景羟基磷灰石（HAP）是大多数特发性草酸钙（CaOx）结石的常见成分，常用作诱发CaOx肾结石形成的病灶。方法比较研究了4种不同粒径（40 nm ~ 2 μm）的HAP晶体（HAP-40 nm、HAP-70 nm、HAP-1 μm和HAP-2 μm）对人近端肾小管上皮细胞（HK-2）的细胞毒性。结果HAP晶体以浓度依赖性方式降低HK-2细胞的活力和膜完整性，导致细胞骨架损伤、细胞肿胀、细胞内活性氧水平升高、线粒体膜电位降低、细胞内钙离子浓度升高、细胞周期阻滞并停滞在G 0/G1期，细胞坏死率增加。HAP对HK-2细胞的毒性随着晶体尺寸的减小而增加。结论HAP晶体引起的细胞损伤增加了肾结石形成的风险。
Background Hydroxyapatite (HAP) is a common component of most idiopathic calcium oxalate (CaOx) stones and is often used as a nidus to induce the formation of CaOx kidney stones. Methods This work comparatively studies the cytotoxicity of four kinds of HAP crystals with different sizes (40 nm to 2 μm), namely, HAP-40 nm, HAP-70 nm, HAP-1 μm, and HAP-2 μm, on human renal proximal tubular epithelial cells (HK-2). Results HAP crystals reduce the viability and membrane integrity of HK-2 cells in a concentration-dependent manner and consequently cause cytoskeleton damage, cell swelling, increased intracellular reactive oxygen species level, decreased mitochondrial membrane potential, increased intracellular calcium concentration, blocked cell cycle and stagnation in G0/G1 phase, and increased cell necrosis rate. HAP toxicity to HK-2 cells increases with a decrease in crystal size. Conclusion Cell damage caused by HAP crystals increases the risk of kidney stone formation.