优克龙对肾脏草酸钙晶体形成的影响及机制
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国家自然科学基金(81870512,81900684)


The effect and mechanism of urocalum on the formation of renal calcium oxalate crystals
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    摘要:

    目的:探讨优克龙对肾脏草酸钙结石形成的影响及机制。方法:采用乙二醇、氯化铵以及葡萄糖酸钙联合诱导大鼠,构建大鼠肾脏草酸钙结石模型。优克龙干预上述模型4周,收集尿液、肾脏组织行HE染色,尿液中生化成分检测,肾脏组织中自噬与凋亡关键蛋白的水平检测。采用草酸钙结晶与肾小管上皮细胞联合培养,构建草酸钙结石细胞模型。α-硫辛酸干预上述细胞模型,探讨草酸钙结晶诱导肾小管上皮细胞发生氧化应激的机制;采用优克龙干预上述细胞模型,探究优克龙保护肾小管上皮细胞的作用及分子机制。结果:动物实验中,与对照组相比,模型组草酸钙结石数量显著升高,而优克龙可显著抑制草酸钙结石的形成,这一效应可能与降低氧化应激水平、自噬与细胞凋亡水平有关。在细胞模型中,α-硫辛酸可显著抑制由草酸钙结晶诱导的肾小管上皮细胞氧化应激过程,细胞自噬与凋亡水平均显著下降,提示细胞发生氧化应激后激活了细胞自噬与凋亡水平;优克龙也可抑制氧化应激过程,细胞中MAPK通路激活水平显著下降,细胞自噬与凋亡水平均明显抑制。结论:优克龙可显著抑制肾脏草酸钙结石的形成,并可抑制由草酸钙结晶诱导的细胞氧化应激过程,通过MAPK通路明显降低细胞的自噬与凋亡水平。

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    Objective:This study aims to investigate the effects and mechanism of urocalum on the formation of kidney calcium oxalate stones. Methods:A rat model with renal calcium oxalate stone was constructed. Urocalum was intervened in this model for four weeks and renal samples were collected for HE staining,while urine samples were collected for the examination of biochemical components. In addition,autophagy and apoptotic key proteins were detected in renal tissues. A model of calcium oxalate stone cells was constructed by calcium oxalate crystallization in tubular epithelial cells. The cell model was treated with urocalum to explore the protective effect and molecular mechanism of urocalum on renal tubular epithelial cells. Results:The number of calcium oxalate stones was significantly increased compared to the control group. Whereas,urocalum could significantly inhibit the formation of stones,which may be associated with reducing oxidative stress levels,autophagy and apoptosis levels. In the cell model,α-sulphpoic acid can significantly inhibit the renal cell oxidative stress process induced by calcium oxalate crystallization,and both cell autophagy and apoptosis levels were activated after oxidative stress. Urocalum can also inhibit the oxidative stress process,while the phosphorylation of MPAK signaling pathway was significantly reduced and levels of autophagy and apoptosis were remarkably lowered. Conclusion:Urocalum can significantly inhibit the formation of renal calcium oxalate stones,and attenuate the oxidative stress process induced by calcium oxalate crystallization,and significantly reduce autophagy and apoptosis through the MAPK signaling pathway.

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鲁 佩,宋日进,张 炜,郑 明,桂泽平,王子杰,王增军,顾 民.优克龙对肾脏草酸钙晶体形成的影响及机制[J].南京医科大学学报(自然科学版),2021,(11):1569-1573

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  • 收稿日期:2021-07-23
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  • 在线发布日期: 2021-12-13
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