Bittolo-Bon G, Cazzolato G, Avogaro P
Regional Centre for Atherosclerosis, Regional General Hospital, Venice, Italy.
Pharmacol Res. 1994 May-Jun;29(4):337-44. doi: 10.1016/1043-6618(94)80055-3.
Twelve patients with primary hypercholesterolemia were treated for 12 weeks with probucol (500 mg b.i.d.). For each patient low density lipoproteins (LDL), isolated by ultracentrifugation were subfractionated by ion exchange high resolution chromatography in order to evaluate the content of a more electronegatively charged LDL (LDL-), a small subfraction that probably represent a circulating oxidatively modified lipoprotein. The treatment induced a 17% reduction of total LDL and 43% reduction of LDL-. By thin layer chromatography the probucol content in LDL- was a quarter of that in normally charged LDL. Under basal conditions, native LDL incubated for 24 h with 3 microM copper sulphate shows a net increase in electrophoretic mobility, an increase in relative fluorescence intensity and a reduction in vitamin E content, thus indicating peroxidative damage. After treatment with probucol, no significant changes of electrophoretic mobility, fluorescence and vitamin E content are detectable. LDL isolated from patients treated with probucol thus become resistant to oxidation by copper ions. The observed reduction of LDL- after treatment with probucol, confirms in vivo the antioxidant role of the drug and support the hypothesis that circulating LDL- may be linked to an oxidative process occurring in vivo.
12例原发性高胆固醇血症患者接受了12周的普罗布考治疗（500毫克，每日两次）。对于每例患者，通过超速离心分离得到的低密度脂蛋白（LDL），再通过离子交换高分辨率色谱法进行亚组分分离，以评估带更多负电荷的LDL（LDL-）的含量，这是一个小亚组分，可能代表循环中的氧化修饰脂蛋白。该治疗使总LDL降低了17%，LDL-降低了43%。通过薄层层析法测定，LDL-中的普罗布考含量是正常电荷LDL中的四分之一。在基础条件下，天然LDL与3 microM硫酸铜孵育24小时后，电泳迁移率净增加、相对荧光强度增加且维生素E含量降低，从而表明发生了过氧化损伤。用普罗布考治疗后，未检测到电泳迁移率、荧光和维生素E含量有显著变化。因此，从接受普罗布考治疗的患者中分离出的LDL对铜离子氧化具有抗性。普罗布考治疗后观察到的LDL-降低，在体内证实了该药物的抗氧化作用，并支持了循环LDL-可能与体内发生的氧化过程有关的假说。
