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从肾结石中获取的天然生成晶体对肾小管上皮细胞的损伤小于合成晶体。

Naturally produced crystals obtained from kidney stones are less injurious to renal tubular epithelial cells than synthetic crystals.

作者信息

Escobar Carla, Byer Karen J, Khan Saeed R

机构信息

Department of Pathology, College of Medicine, University of Florida, Gainesville, Florida, USA.

出版信息

BJU Int. 2007 Oct;100(4):891-7. doi: 10.1111/j.1464-410X.2007.07002.x. Epub 2007 Jun 6.

Abstract

OBJECTIVE

To determine the differences in cell responses to synthetic and biological crystals of calcium oxalate (CaOx) and brushite

MATERIALS AND METHODS

Nephrolithiasis depends on crystal retention within the kidneys, often promoted by crystal attachment to the injured renal epithelium; studies often use various crystals that might be injurious to cells and cause the exposure of crystal binding molecules on cell surfaces, thus promoting crystal attachment and retention. The synthetic crystals used in these studies might be more injurious than the biological crystals naturally produced in the kidneys and that form kidney stones. We exposed the renal epithelial cell line NRK 52E in vitro to CaOx or brushite crystals at 67 or 133 microg/cm(2) for 3 or 6 h. Synthetic crystals were purchased and the biocrystals were obtained by pulverizing CaOx and brushite stones. We determined the release of lactate dehydrogenase (LDH), hydrogen peroxide (H(2)O(2)) and 8-isoprostane (8-IP), and monocyte chemoattractant protein-1 (MCP-1), as markers of injury, oxidative stress and inflammation, respectively. Cells were also examined after trypan blue staining to determine their membrane integrity. We also examined crystals of CaOx by scanning electron microscopy both in the native state as well as after decalcification.

RESULTS

Exposure to both the synthetic and biological crystals resulted in a significant increase in LDH release and trypan blue staining, as a sign of crystal-induced injury. There was increased production of H(2)O(2) and 8-IP, suggesting the development of oxidative stress. In addition MCP-1 production was also significantly increased. However, the synthetic crystals caused significantly higher increases in all the indicators than the biological crystals.

CONCLUSIONS

These results indicate that even though both synthetic and naturally produced biocrystals invoke a response from the renal epithelial cells, the latter are significantly less injurious and inflammatory. Exposure to low concentrations of these crystals alone might not invoke an inflammatory response, cause the uncovering of crystal binding molecules on epithelial cell surfaces, and promote crystal attachment and retention.

摘要

目的

确定细胞对草酸钙(CaOx)和透钙磷石的合成晶体与生物晶体的反应差异

材料与方法

肾结石取决于晶体在肾脏内的滞留,这通常是由晶体附着于受损的肾上皮所促进;研究中常使用各种可能对细胞有害并导致细胞表面晶体结合分子暴露的晶体,从而促进晶体的附着和滞留。这些研究中使用的合成晶体可能比肾脏中自然产生并形成肾结石的生物晶体更具危害性。我们在体外将肾上皮细胞系NRK 52E暴露于67或133微克/平方厘米的CaOx或透钙磷石晶体中3或6小时。合成晶体购自市场,生物晶体通过粉碎CaOx和透钙磷石结石获得。我们分别测定了乳酸脱氢酶(LDH)、过氧化氢(H₂O₂)和8-异前列腺素(8-IP)以及单核细胞趋化蛋白-1(MCP-1)的释放,它们分别作为损伤、氧化应激和炎症的标志物。细胞经台盼蓝染色后也进行了检查以确定其膜完整性。我们还通过扫描电子显微镜检查了天然状态以及脱钙后的CaOx晶体。

结果

暴露于合成晶体和生物晶体均导致LDH释放和台盼蓝染色显著增加,这是晶体诱导损伤的标志。H₂O₂和8-IP的产生增加,表明氧化应激的发展。此外,MCP-1的产生也显著增加。然而,合成晶体在所有指标上引起的增加均显著高于生物晶体。

结论

这些结果表明,尽管合成晶体和天然产生的生物晶体均会引起肾上皮细胞反应,但后者的危害性和炎症性明显较小。单独暴露于低浓度的这些晶体可能不会引发炎症反应、导致上皮细胞表面晶体结合分子的暴露以及促进晶体的附着和滞留。

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