暴一众 王 丹 胡昱兴 徐爱红 孙梅贞 陈红红. 螯合剂BPCBG对铀的促排效果和防护铀致人肾小管上皮细胞损伤的作用J. 药学学报, 2011,46(11): 1308-1313.
引用本文: 暴一众 王 丹 胡昱兴 徐爱红 孙梅贞 陈红红. 螯合剂BPCBG对铀的促排效果和防护铀致人肾小管上皮细胞损伤的作用J. 药学学报, 2011,46(11): 1308-1313.
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BAO Yi-Yin, WANG Dan, HU Yu-Xin, XU Ai-Gong, SUN Mei-Zhen, CHEN Gong-Gong. Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitroJ. 药学学报, 2011,46(11): 1308-1313.
Citation: BAO Yi-Yin, WANG Dan, HU Yu-Xin, XU Ai-Gong, SUN Mei-Zhen, CHEN Gong-Gong. Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitroJ. 药学学报, 2011,46(11): 1308-1313.
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螯合剂BPCBG对铀的促排效果和防护铀致人肾小管上皮细胞损伤的作用

Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro

    摘要
  • 摘要:

    从动物和细胞水平观察螯合剂N, N '-1, 2-亚乙基双N-(2, 3-二羟基苯甲基)甘氨酸 (BPCBG) 对铀的促排效果, 以及对铀致人肾近曲小管上皮细胞 (HK-2) 损伤的保护作用。大鼠腹腔注射 (ip) 醋酸铀酰后立即肌内注射 (im) 不同剂量的BPCBG , 采用ICP-MS方法测定24 h的尿铀排出量和肾、骨中铀蓄积量。人肾近曲小管上皮HK-2细胞染铀24 h后给予不同剂量的BPCBG作用24 h, 采用ICP-MS方法检测细胞内铀含量。不同剂量醋酸铀酰染毒HK-2细胞后立即或延迟24 h给予BPCBG作用24或48 h, 采用CCK-8试剂盒检测细胞存活率, 采用CB微核法观察BPCBG对铀致染色体损伤的影响, 采用DCFH-DA荧光探针法检测BPCBG 对铀诱导细胞内氧自由基生成的影响。以上实验均以DTPA-CaNa3作对照。结果表明, BPCBG (60、120和600 μmol·kg−1) 使24 h尿铀排出量较铀中毒对照组明显增加约37%～61%, 肾、骨中铀蓄积量降低至中毒对照组的41%～31%和86%～42%, 促排效果随给药剂量增加而明显增强。HK-2细胞铀染毒后延迟24 h给予10～250 μmol·L−1 BPCBG作用24 h, 使细胞内铀含量较铀染毒组显著降低约55%～60%, 并能明显提高铀染毒HK-2细胞的存活率, 显著降低铀诱导的微核形成, 有效抑制铀诱导的细胞内氧自由基的产生。DTPA-CaNa3虽能明显降低大鼠肾铀蓄积量和细胞内铀含量, 但促排效果显著低于BPCBG, 且对铀致细胞损伤无保护作用。以上动物和细胞实验均证明BPCBG是有效的铀促排剂, 明显优于DTPA-CaNa3, 并具有清除铀诱导细胞内氧自由基产生的作用, 可以保护铀致肾细胞损伤, 值得进一步研究。

     

    Abstract:

    This study is to assess the efficacy of BPCBG on the decorporation of uranium (Ⅵ) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage.  BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2.  Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS.  After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) oxidation.  DTPA-CaNa3 was used as control.  It was found that BPCBG at dosages of 60, 120, and 600 μmol·kg−1 resulted in 37%−61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%−31% and 86%−42% of uranium-treated group, respectively.  After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%−60% of the intracellular uranium was removed by 10−250 μmol·L−1 of BPCBG.  Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS.  Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG, and it could not protect uranium-induced cell damage.  It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3.  It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage.  BPCBG is worth further investigation.

     

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