细胞铁代谢变化参与阿司匹林抗氧化作用的调控机制

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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 investigate the regulatory role of ferritin (Fn) expression and intracellular iron changes in the anti-oxidative damage of aspirin (AS). Methods: The expression of Fn induced by different concentrations of AS was detected by ELISA. The effect of FeCl3 and deferoxamine on the expression of Fn was also observed. The expression of IRP was detected by RNA-protein bandshiftassay and RT-PCR. Activity and IRP2 mRNA level changes. RESULTS: 0 1 mmol / L AS induced a more than 25% Fn expression in endothelial cells. With the increase of AS dose, the expression of Fn gradually increased, with a significant dose-dependent relationship. AS induced Fn expression can significantly enhance the ability of cells to resist H2O2 injury. However, the expression of Fn in deferoxamine + AS group was significantly decreased, the binding activity of IRP was 3 times normal and the expression of IRP2 mRNA was also increased. However, the expression of Fn in FeCl3 + AS group was significantly higher than that in deferoxamine group However, the binding activity of IRP decreased and the expression of IRP2 mRNA decreased. CONCLUSIONS: Aspirin exerts anti-oxidative effects by down-regulating IRP binding activity and IRP2 mRNA levels, resulting in increased expression of ferritin.
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