螯合剂对铀在小鼠体内分布的影响研究

铀在生物体内的化学形态及分布是评价铀毒性的基础。文章通过尾静脉注射给药方式研究螯合剂对染铀小鼠体内铀分布的影响。通过建立包含主要体液金属离子、小分子配体及UO₂²⁺与螯合剂的热力学平衡模型，采用数值模拟方法研究UO₂²⁺在血液中的形态。实验结果表明：DTPA易与UO₂²⁺形成［(UO₂)₂(OH)DTPA］^2-，对小鼠血液中的UO₂²⁺有明显的促排作用，但在促排的同时对小鼠的肾脏和骨骼有损伤；抗坏血酸对小鼠体内各组织器官的铀促排几乎无作用，但形成的［(UO₂)₂(OH)Ascorbate］²⁺会阻碍肾脏中U(Ⅵ)的代谢；NTA对小鼠体内各组织器官铀的促排作用小，并会促使体内出现固相(UO₂)₃(PO₄)₂·4H₂O，对骨骼有较强的损伤作用，不适合作为铀的促排剂。

Influence of Chelating Agents on Bio-distribution of Uranium in Mice

Tissue distribution of UO₂²⁺ in mice was investigated with dose of 5 mgU/kg and different chelating agents. A thermodynamic equilibrium model, involved in major metal-ions, low molecular weight molecule ligands and chelating agents, was made to analyze the speciation of UO₂²⁺ in human fluid. Computer simulation indicates that UO₂²⁺ will easily exist as ［(UO₂)₂(OH)DTPA］^2- species when the presence of DTPA and UO₂²⁺ in the blood of mice can be significantly removed out, but to some extent will damage kidneys and bones at same time. In contrast, ascorbic acid prevents ordinary metabolism of uranium in kidneys of mice, without any effect on removal of uranium, unfortunately, the complex compound of UO₂²⁺ ion with ascorbic acid is ［(UO₂)₂(OH)Ascorbate］²⁺  which will affect UO₂²⁺ normal removal from kidneys. It can be concluded that NTA has a little effect on removal of uranium in tissues and organs of mice and promote the UO₂²⁺ and PO₄^3- ion from solid phase as (UO₂)₃(PO₄)₂·4H₂O which will deposit on the bone surface.