上海交通大学学报（医学版）

›› 2009, Vol. 29 ›› Issue (12): 1474-.

• 论著（基础研究） • 上一篇    下一篇

钙拮抗剂对高草酸尿导致的大鼠肾小管上皮细胞损伤的保护作用

李文峰, 张士青   

  1. 上海交通大学 医学院第三人民医院泌尿外科, 上海 201900
  • 出版日期:2009-12-25 发布日期:2009-12-25
  • 作者简介:李文峰（1978—）, 男, 主治医师, 硕士；电子信箱: lichen0612@163.com。

Preventive effects of calcium antagonist on injury of renal tubular epithelial cells induced by hyperoxaluria

LI Wen-feng, ZHANG Shi-qing   

  1. Department of Urology, The Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, China
  • Online:2009-12-25 Published:2009-12-25

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摘要：

目的 观察高草酸尿对大鼠肾小管上皮细胞内游离钙离子浓度 ([Ca2+]i)和细胞凋亡的影响，并了解钙拮抗剂硝苯地平对该影响的保护作用。方法 60只雄性SD大鼠随机分成饮水组（只饮去离子水)、硝苯地平组（饮去离子水，并灌喂硝苯地平10 mg·kg-1·d-1）、诱石组（饮1%乙二醇去离子水）、诱石＋硝苯地平干预组（共3组，饮1%乙二醇去离子水，并分别灌喂硝苯地平 3、6、10 mg·kg-1·d-1），每组10只，连续处理4周。测定各组大鼠24 h尿草酸浓度；TUNEL技术检测肾小管上皮细胞凋亡指数；应用Flou-3/AM荧光指示剂测定大鼠肾近曲小管细胞内Ca2+的荧光强度。结果 诱石组和诱石＋硝苯地平干预组24 h尿草酸浓度均高于饮水组和硝苯地平组（P<0.01）。与饮水组相比，诱石组大鼠肾小管上皮细胞凋亡指数和肾小管上皮细胞内Ca2+荧光强度均明显增加（P<0.01）。诱石＋硝苯地平(3、6、10 mg·kg-1·d-1)干预组Ca2+荧光强度分别为诱石组的76.7％、62.7％和56.4％，量效关系显著（r＝0.839，P<0.01）。肾小管上皮细胞内Ca2+荧光强度与肾小管上皮细胞凋亡指数密切相关（r＝0.826，P<0.01）。结论 高草酸尿可使大鼠肾小管上皮细胞[Ca2+]i及细胞凋亡水平显著增加，钙拮抗剂硝苯地平对此有明显的干预效果。

关键词: 肾, 草酸, 钙, 细胞凋亡, 硝苯地平

Abstract:

Objective To investigate the effects of hyperoxaluria on rat renal tubular epithelium intracellular calcium concentration ([Ca2+]i) and cell apoptosis, and explore the protective effects of calcium antagonist-nifedipine. Methods Sixty male SD rats were randomly divided into six groups (n=10). Rats in water-drinking group were treated with deionized water, nifedipine group with deionized water and nifedipine 10 mg·kg-1·d-1, calculiinduced group with deionized water containing 1% ethylene glycol, and three calculi-induced+nifedipineintervening groups with deionized water containing 1% ethylene glycol plus nifedipine 3, 6 and 10 mg·kg-1·d-1, respectively. Four weeks later, the 24 h oxaluria concentration was measured, the apoptosis index of renal tubular epithelial cells was detected with TUNEL method, and Ca2+ fluorescence intensity of cells of renal proximal tubules was determined by flow cytometry using Fluo-3/AM staining. Results The 24 h oxaluria concentrations in calculi-induced group and calculi-induced+nifedipine-intervening groups were higher than those in water-drinking group and nifedipine group （P＜0.01）. The apoptosis index and Ca2+ fluorescence intensity were significantly higher in calculi-induced group than those in water-drinking group （P<0.01）. The Ca2+ fluorescence intensity in calculi-induced+nifedipine (3, 6 and 10 mg·kg-1·d-1)-intervening groups was 76.7％, 62.7％ and 56.4％ of calculi-induced group, respectively, with a significant dose-effect relationship (r=0.839, P<0.01). The apoptosis index of renal tubular epithelial cells was significantly correlated with Ca2+ fluorescence intensity (r=0.826, P<0.01). Conclusion Hyperoxaluria can increase apoptosis and \[Ca2+\]i concentration of renal tubular epithelial cells in rats, and nifedipine can effectively protect renal tubular epithelial cells to resist hyperoxaluria.

Key words: kidney, oxalate, calcium, apoptosis, nifedipine