Inhibitory Effect of Isorhapontigenin on Copper-Mediated Peroxidation of Human Low-Density Lipoprotein in vitro  

异丹叶大黄素在体外对Cu^(2+)介导的人低密度脂蛋白过氧化的抑制作用(英文)

作　　者：方亚南[1] 林茂[1] 刘耕陶[1] 

机构地区：[1]中国医学科学院

出　　处：《Journal of Chinese Pharmaceutical Sciences》2004年第1期63-67,共5页中国药学（英文版）

摘　　要：Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.目的　研究异丹叶大黄素 (Iso)对Cu2 + 介导的人低密度脂蛋白 (LDL)过氧化及氧化LDL(ox LDL)对小鼠巨噬细胞毒性的抑制作用。方法　用序贯超离心法分离血脂正常的供血者血清LDL ,分离的LDL 1mg·mL- 1磷酸缓冲液 (pH 7 4) ,与 10μmol·L- 1CuSO4 于 3 7℃水浴温育 10h以引起LDL过氧化 ,给药组预先加入不同浓度Iso ,对照组加等量生理盐水 ,测定丙二醛(MDA)的生成量、维生素E的耗竭以及LDL电泳迁移率。另外测定用ox LDL处理小鼠腹腔巨噬细胞线粒体的膜电位、吞噬刚果红及释放NO的量。结果　 1-10 0 μmol·L- 1Iso剂量依赖性地抑制Cu2 + 引起的人LDL氧化时MDA的生成量、维生素E的耗竭及电泳迁移率的升高。 10 μmol·L- 1Iso能防止 0 1mg·mL- 1ox LDL与小鼠腹腔巨噬细胞温育 4h后线粒体膜电位的损伤、吞噬刚果红功能以及NO释放量的降低。结论　Iso在体外对Cu2 + 介导的LDL过氧化以及ox LDL对小鼠巨噬细胞的毒性有保护作用。

关 键 词：ISORHAPONTIGENIN low-density lipoprotein oxidized low-density lipoprotein MACROPHAGES PHAGOCYTOSIS mitochondrial membrane potential 

分 类 号：R285[医药卫生—中药学]