细胞铁代谢变化参与阿司匹林抗氧化作用的调控机制  

Regulatory mechanism of cellular iron metabolism on aspirin resistance to oxidative damage

作　　者：何志旭[1] 廖清奎[2] 周同甫[2] 徐学聚[2] 罗春华[2] 李钦伯[2] 李丰益[2] 王树人[3] 

机构地区：[1]中山医科大学附二院儿科,广东广州510120 [2]华西医科大学附二院铁营养及血液肿瘤研究室,四川成都610041 [3]华西医科大学病理生理教研室,四川成都610041

出　　处：《中国病理生理杂志》2002年第2期136-139,共4页Chinese Journal of Pathophysiology

摘　　要：目的 :探讨铁蛋白 (Fn)表达及细胞内铁的变化在阿司匹林 (AS)抗氧化损伤中的调控作用。方法 :ELISA法检测不同浓度AS诱导Fn的表达 ,以及FeCl3和去铁胺对AS诱导Fn表达的影响 ;同时使用RNA -proteinbandshiftassay及RT -PCR检测AS诱导铁蛋白表达过程中铁调节蛋白 (IRP)结合活性及IRP2 mRNA水平的变化。结果 :0 1mmol/L的AS可诱导内皮细胞Fn表达超过对照 2 5 % ,随AS剂量的增大诱导Fn表达逐渐增加 ,二者间有明显的剂量依赖关系。AS诱导Fn表达后能明显增强细胞抗H2 O2 损伤的能力。但去铁胺 +AS组细胞Fn表达明显降低 ,此时IRP的结合活性却为正常的 3倍 ,IRP2 mRNA的表达水平也升高 ;而FeCl3+AS组Fn表达明显高于去铁胺组 ,但IRP的结合活性降低、IRP2 mRNA表达水平下降。结论 :阿司匹林通过下调IRP结合活性及IRP2 mRNA水平 ,导致细胞铁蛋白表达增加而发挥抗氧化损伤的作用。AIM: To explore the regulatory effects of ferritin expression and intracellular iron change on aspirin resistance to oxidative damage in endothelial cells. METHODS: Using ELISA to measure the levels of ferritin expression under different aspirin concentrations, in the presence of iron cheltor desferioxamine and add to FeCl 3. Then using RNA-protein bandshift assay and RT-PCR to examine the activation of IRP and the expression of IRP 2 mRNA onaspirin induced ferritin formation. RESULTS: Aspirin at low concentration (0.1mmol/L) induced significant increase in ferritin expression in a concentration-dependent fashion up to 25% over basal levels. Aspirin induced cytoprotection from H 2O 2 damage increased significantly following ferritin formation in endothelial cells.However, in the presence of iron chelator desferrioxamine, aspirin enhanced ferritin synthesis was abrogated with a 3 fold increase in the activity of IRP and significant increase in IRP 2 mRNA level. In contrast, FeCl 3 and aspirin both increased the level of induced ferritin synthesis with significant decrease in IRP activity and IRP 2 mRNA level. CONCLUSION: The effect of aspirin induced ferritin synthesis on resistance to oxidative damage in endothelium was operated through down-regulating IRP activation and IRP 2 mRNA level.

关 键 词：阿司匹林 抗氧化药 铁蛋白 

分 类 号：R978.11[医药卫生—药品] R363.22[医药卫生—药学]