The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis

    PQRST研究了降脂与抗氧化药物普罗布考对人动脉粥样硬化进程的影响。303例高胆固醇血症患者随机分组分别接受普罗布考和安慰剂治疗，联合建议饮食与消胆胺治疗3年。未发现普罗布考对股动脉粥样硬化的进展有显著性疗效。评价抗氧化剂普罗布考在试验中的疗效，对42名随机选取的患者进行详细分析。与对照组相比，普罗布考治疗患者（n=26）总胆固醇含量下降15%（P< 0.01），高密度脂蛋白胆固醇下降35%(P < 0.0001)。通过测定延迟期双烯烃的形成，与对照组相比，普罗布考治疗患者的低密度脂蛋白对Cu²⁺诱导的氧化呈现出更强的抵制性。脂质过氧化降低13倍，巨噬细胞恶化降低97%，氧化后的LDL受体的粘附下降近90%。结果表明，尽管普洛布考对Cu²⁺诱导的LDL氧化修饰呈现出较强的保护作用，但对股动脉粥样硬化进展无疗效。

    The Probucol Quantitative Regression Swedish Trial (PQRST) investigated the effect of the lipid lowering and         antioxidant drug probucol on the development of atherosclerosis in humans. 303 hypercholesterolemic patients were        randomized to receive either probucol or placebo, in combination with dietary advice and cholestyramine for a three-year period. Probucol was not found to effect progression regression of femoral atherosclerosis significantly as assessed by  quantitative arteriography. To evaluate the effectiveness of probucol as an antioxidant during the study period, detailed analyses were performed on 42 of the randomized patients. During the trial, probucol-treated patients (n = 26) had 15%   lower total cholesterol (P < 0.01) and 35% lower high density lipoprotein (HDL) cholesterol (P < 0.0001) compared with   controls (n = 16). Low density lipoprotein (LDL) from probucol treated individuals was more resistant to oxidation by Cu²⁺ as determined by the lag phase for the formation of conjugated dienes (220 +/- 8 vs. 82 +/- 7 min (mean +/- S.E)), showed a 13 times lower formation of lipid peroxides, a 97% reduction in macrophage degradation and close to 90% less decrease  in LDL receptor binding following oxidation as compared with controls (P < 0.001 for all differences). The results       demonstrate that although probucol provided a significant protection against Cu²⁺-induced oxidative modification of LDL,  it lacked effect on the development of femoral atherosclerosis. The relevance of these observations for the proposed role of lipid oxidation in atherosclerosis is discussed.