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目的:研究Ebselen对Cu2+、Fe2+及巨噬细胞氧化修饰人低密度脂蛋白(LDL)的抑制作用及其可能机制。方法:采用紫外分光光度法检测人LDL中硫代巴比妥酸反应物(TBARS)及共轭双烯(CD)的含量来表示LDL的被氧化程度。结果:Cu2+、Fe2+及体外培养的小鼠腹腔巨噬细胞(MPM)都能氧化修饰人LDL,使其中的TBARS和CD含量显著升高。Ebselen(0.5~4.0μmol/L)能剂量依赖性降低人LDL中TBARS和CD含量,其中2μmol/L的Ebselen能完全抑制Cu2+、Fe2+及MPM升高LDL中TBARS含量的作用。单用谷胱甘肽(GSH,0.5mmol/L)对LDL中TBARS含量没有显著的影响,但GSH能显著增强Ebselen对TBARS生成的抑制作用。结论:Ebselen能抑制Cu2+、Fe2+及MPM氧化修饰人LDL,GSH能明显增强Ebselen的这种抑制作用。
Objective: To study the inhibitory effect of Ebselen on oxidized low density lipoprotein (LDL) in Cu2 +, Fe2 + and macrophages and its possible mechanism. Methods: UV-Vis spectrophotometry was used to determine the degree of oxidation of LDL by detecting the content of thiobarbituric acid reactants (TBARS) and conjugated dienes (CDs) in human LDL. Results: Both Cu2 +, Fe2 + and mouse peritoneal macrophages (MPM) cultured in vitro could oxidatively modify human LDL and the contents of TBARS and CD in them were significantly increased. Ebselen (0.5 ~ 4.0μmol / L) could reduce TBARS and CD in human LDL in a dose-dependent manner. Ebselen at 2μmol / L could completely inhibit the effect of Cu2 +, Fe2 + and MPM on TBARS in LDL. Glutathione alone (GSH, 0.5 mmol / L) had no significant effect on the TBARS content in LDL, but GSH significantly enhanced the inhibitory effect of Ebselen on TBARS production. Conclusion: Ebselen can inhibit the oxidative modification of human LDL by Cu2 +, Fe2 + and MPM. GSH can significantly enhance this inhibitory effect of Ebselen.