D-青霉胺和二巯丙磺酸钠对汞致大鼠肾毒性的影响  

Effect of D-penicillamine and 2,3-dimercaptopropane-1-sulfonate attenuating acute nephrotoxicity induced by mercuric chloride in rats

作　　者：尹忠伟[1] 徐兆发[1] 杨敬华[1] 于佳明[1] 孙炜[1] 李晶[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2005年第1期32-34,共3页Journal of Toxicology

基　　金：辽宁省自然科学基金项目 (962 32 8)

摘　　要：目的　研究预投D- 青霉胺 (D- penicillamine ,DPA)和二巯丙磺酸钠 (2 ,3 - Dimercato 1 Propanesulfonate ,DMPS)对汞致急性肾毒性的保护作用及其机制。方法　 48只Wistar大鼠随机分成 6组。第 1组以 5mL/kg体重皮下注射质量分数为 0 . 9%的氯化钠溶液 ,第 2、3和 4组分别皮下注射 0 .75、1.5和 2 .5mg kgHgCl2 溶液。第 5、6组大鼠分别腹腔注射2 0 0 μmoLDMPS和 2 0 0 μmoLDPA ,2h后再投与 2 5mg/kgHgCl2 溶液。染毒 12h后 ,收集 12h尿样 ,测定尿N- 乙酰 - β- D- 氨基葡萄糖苷酶 (NAG)和尿碱性磷酸酶 (ALP)活力、尿蛋白和尿汞含量。染毒 48h后 ,切取肾脏和肝脏 ,分别测定肾脏和肝脏中的丙二醛 (MDA)和谷胱甘肽 (GSH)含量、谷胱甘肽过氧化物酶 (GSH- Px)活力、肝脏汞和肾脏汞含量。结果　DMPS显著降低NAG和ALP活力和尿蛋白含量 ;DPA明显降低NAG活力和尿蛋白含量 ,对ALP没有影响。DMPS显著降低肾脏MDA含量 ,而DPA对肾脏MDA含量没有影响。DMPS-和DPA两干预组在肾脏中GSH含量和GSH -Px活力都明显高于 2 . 5mg kg染汞组 ,差异有显著性。DPA能显著降低肾脏汞含量。结论　DMPS比DPA更能有效地保护肾功能。DMPS会显著减轻汞在肾脏的氧化损伤 ,而DPA则没有影响。DMPS和DPA能明显减少肾脏GSH和GSH-Objective To study the mechanism on nephrotoxi city of mercury(Hg) and the preventive effect of 2,3-dimercaptopropane-1-sulf onate (DMPS) and D-penicillamine (DPA) attenuating acute toxicity of mercuric c hloride (HgCl\-2).Methods 48 Wistar rats were randomly divided into 6 groups.The first group was injected subcutaneously with 0.9% saline. The rats in next thre e groups were respectively subcutaneously injected with 0.75, 1.5, 2.5 mg/kg H gCl\-2.Pretreated with DMPS and DPA respectively 2 hours earlier, The rats in th e fifth and sixth group were given an injection with 2.5 mg/kg HgCl\-2. After b eing treated 12 hours later, the urine was collected.And the activities of urina ry N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP), the co ntents of urinary protein and urinary Hg were determined. All rats were anatomiz ed 48 hours later and the liver and kidney were excised. Then renal Hg and hepat ic Hg were determined.Results DMPS decreased the contents of malondialdehyde (MDA) an d glutathione (GSH),the activities of glutathione peroxidase (GSH-Px), the acti vities of urinary NAG and urinary ALP and the content of urinary protein. Althou gh DPA mitigated the activities of urinary NAG and the content of urinary protei n significantly,it had no effect on the activities of urinary ALP.Both the conte nt of GSH and activities of GSH-Px of the DMPS and DPA preventive group were si gnificantly higher in the kidney and liver than those of 2.5 mg/kg Hg group.DPA reduced the content of renal Hg significantly.Conclusion DMPS can more efficiently prevent the nephrotoxicity of H g than DPA.DMPS can significantly attenuate the lipid peroxidation in kidney,how ever DPA has no effect.Both DMPS and DPA can significantly diminish the depletio n of gSH and GSH-Px.DPA results in the redistribution of Hg from the kidney to other tissues and organs,however the redistribution of Hg doesn't occur to DMPS.

关 键 词：二巯丙磺酸钠 D-青霉胺 尿N-乙酰-β-D-氨基葡萄糖苷酶 谷胱甘肽过氧化物酶(GSH-Px) Wistar大鼠 丙二醛(MDA) GSH-PX活力 DMPS HgCl2 尿蛋白含量 MDA含量 DPA 皮下注射 急性肾毒性 氯化钠溶液 碱性磷酸酶 GSH含量 汞含量 

分 类 号：R979.3[医药卫生—药品] R978.11[医药卫生—药学]