中华放射医学与防护杂志

王丹,暴一众,胡昱兴,等.螯合剂BPCBG对急性铀中毒大鼠的促排效果及肾损伤的保护作用[J].中华放射医学与防护杂志,2012,32(4):337-341.WANG Dan,BAO Yi-zhong,HU Yu-xing,et al.The chelator BPCBG decorporates uranium and protects against uranium-induced kidney injury in rats[J].Chin J Radiol Med Prot,2012,32(4):337-341

螯合剂BPCBG对急性铀中毒大鼠的促排效果及肾损伤的保护作用

The chelator BPCBG decorporates uranium and protects against uranium-induced kidney injury in rats

投稿时间：2012-04-28

DOI：10.3760/cma.j.issn.0254-5098.2012.04.001

中文关键词: BPCBG 铀螯合剂促排肾损伤大鼠

英文关键词:BPCBG Uranium Chelating agent Decorporation Kidney injury Rats

基金项目:国家自然科学基金(30970870)

作者	单位	E-mail
王丹	200032 上海, 复旦大学放射医学研究所
暴一众	200032 上海, 复旦大学放射医学研究所
胡昱兴	200032 上海, 复旦大学放射医学研究所
徐爱红	200032 上海, 复旦大学放射医学研究所
陈红红	200032 上海, 复旦大学放射医学研究所	hhchen@shmu.edu.cn

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中文摘要:

目的探讨螯合剂BPCBG对急性铀中毒大鼠促排作用的量-效和时-效关系以及对铀致肾损伤的保护作用。方法 Sprague-Dawley(SD)雄性大鼠按随机数字表法分为正常对照组、铀中毒组、不同剂量BPCBG组和DTPA-CaNa₃组。给药组大鼠于腹腔注射醋酸铀酰(100 μg/只)后,立即分别肌肉注射60、120和600 μmol/kg BPCBG及120和600 μmol/kg DTPA-CaNa₃,或于注射醋酸铀酰前0.5和2 h、铀中毒后0、0.5、1及2 h肌肉注射120 μmol/kg BPCBG,铀中毒组于注射醋酸铀酰后立即注射等体积生理盐水,正常对照组仅注射生理盐水。采用ICP-MS方法检测24 h尿铀排出量和肾、骨中铀蓄积量。大鼠注射醋酸铀酰(500 μg/只)后立即注射600 μmol/kg BPCBG和1200 μmol/kg DTPA-CaNa₃,48 h后检测血清肌酐(SCR)与尿素氮(BUN)含量,取一侧肾脏做肾组织病理切片观察。结果铀中毒后立即注射不同剂量BPCBG(60、120和600 μmol/kg)使24 h尿铀排出量比铀中毒组增加(t=2.22、4.43、5.80,P<0.05),肾和骨铀蓄积量下降(t=3.33、5.59、4.53,P<0.01和t=2.15、8.70、9.10,P<0.05),随给药剂量增加促排效果明显提高。提前0.5 h或延迟0.5和1 h给予BPCBG,仍有较好的排铀效果(与铀中毒组比较,尿铀排出量:提前0.5 h t=4.34,延迟0.5 h t=3.35,P<0.05;肾铀蓄积量:t=5.75、7.74、5.87,P<0.05;骨铀蓄积量:t=6.43、5.22、2.60,P<0.05),但随铀中毒和给药间隔时间的延长而下降。BPCBG立即给药能明显减轻铀中毒致肾脏的病理损伤,使SCR及BUN含量降低至正常对照组水平,对铀致肾功能损伤具有保护作用。DTPA-CaNa₃虽然能明显降低大鼠肾铀蓄积量(与铀中毒组相比,120和600 μmol/kg,t=2.28、3.35,P<0.05),但未能显著增加尿铀排出量,骨铀蓄积量还有增加趋势,并且对铀致大鼠肾损伤无保护作用。结论 BPCBG对急性铀中毒大鼠有良好的促排效果与肾脏保护作用,有可能成为一种新型铀促排螯合剂。

英文摘要:

Objective To explore the dose- and time-responses of BPCBG on the decorporation of uranium and its protective effects for uranium-induced kidney injury in rats.Methods Sprague-Dawley(SD) male rats were randomly divided into 4-7 groups: normal control group, uranium poisoning group, different doses of BPCBG groups and DTPA-CaNa₃ group. Rats in chelating agents-treated groups were either injected intramuscularly with 60, 120 and 600 μmol/kg of BPCBG or 120 and 600 μmol/kg of DTPA-CaNa₃ immediately after intraperitoneal injection of uranyl acetate dihydrate, or injected with 120 μmol/kg of BPCBG 0.5, 2 h before or 0, 0.5, 1 and 2 h after injection of uranium. Uranium poisoning group rats were injected with normal saline after intraperitoneal injection of uranyl acetate dihydrate, and the normal control group rats were merely injected with normal saline. The uranium content in urine, kidney and femurs were detected 24 h after chelator injections by ICP-MS method. After injecting a dose of 500 μg uranyl acetate dihydrate, rats were injected with 600 μmol/kg of BPCBG or 1200 μmol/kg of DTPA-CaNa₃. Histopathological changes in the kidney and serum creatinine and urea nitrogen were examined 48 h after chelator administration. Results Prompt injections of BPCBG resulted in 37%-61% (t=2.22,4.43,5.80,P<0.05) increase in 24 h-urinary uranium excretion, and significantly decreased the levels of uranium in kidney and bone by 59%-69% (t=3.33,5.59,4.53,P<0.01) and 14%-58% (t=2.15,8.70,9.10,P<0.05) respectively in a dose-dependent manner. BPCBG injection obviously reduced the severity of the uranium-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, serum creatinine and urea nitrogen, of uranium nephrotoxicity. Advanced 0.5 h or delayed 0.5 and 1 h administrations of BPCBG were effective in 24 h-urinary uranium excretion (advanced 0.5 h:t=4.34, delayed 0.5 h: t=3.35, P<0.05), decreasing accumulation of kidney uranium (t=5.75, 7.74, 5.87, P<0.05) and accumulation of bone uranium (t=6.43, 5.22, 2.60, P<0.05), but the efficacy decreased with the interval time between uranium and BPCBG injection. Although DTPA-CaNa₃ markedly reduced uranium retention in kidney(120, 600 μmol/kg,t=2.28, 3.35,P<0.05), its efficacy in uranium removal was significantly lower than that of BPCBG, and it had no protective effects against uranium-induced nephrotoxicity. Conclusions BPCBG can effectively decorporate uranium from rats and protect against uranium-induced kidney injury of rats.

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