【摘要】 目的:观察普罗布考的抗氧化作用以及对高胆固醇血症兔血浆屏氧酶-1含量及肝细胞上屏氧酶-1基因表达的影响,探讨其抗动脉粥样硬化机制。方法:16只纯种雄性新西兰大白兔给予高胆固醇饮食饲养8周后,随机分为:①高胆固醇组(n=8):继续饲以高胆固醇饮食6周;②普罗布考组(n=8):饲以高胆固醇饮食的基础上给予1％普罗布考干预6周。另选普通饮食14周兔(n=8)作为正常组。测定血脂和超氧化物歧化酶活性和丙二醛含量,采用酶联免疫吸附法测定血浆屏氧酶-1的含量,两步灌注消化法进行肝细胞分离和培养,逆转录聚合酶链式反应法测定肝细胞屏氧酶-1信使核糖核酸的表达,苏丹Ⅲ染色测定斑块面积。结果:①高胆固醇组8周后,血浆胆固醇水平明显升高,普罗布考组14周后可明显降低胆固醇的水平(P<0．01);②高胆固醇组8周后,超氧化物歧化酶总活性和丙二醛的含量均升高,14周时普罗布考组丙二醛含量[(9．21±1．31)μg／ml]较高胆固醇组[(12．57±1．43)μg/ml,P<0．01]明显降低;③普罗布考组14周后动脉粥样硬化斑块面积[(51．54±8．32)％]较高胆固醇组[(84．81±9．35)％,P<0．01]明显减少;④14周时普罗布考组屏氧酶-1的含量[(0．85±0．02)μg／ml]较高胆固醇组[(0．51±0．01)μg／ml,P<0．01]明显升高;⑤普罗布考组屏氧酶-1mRNA的表达(0．72±0．01)较高胆固醇组(0．46±0．01,P<0．05)明显增加;⑥血浆屏氧酶-1的含量与丙二醛的含量呈负相关(r=-0．86,P=0．003)。结论:普罗布考具有降脂、抗氧化作用,其抗动脉粥样硬化作用可能是通过影响高密度脂蛋白的抗氧化酶屏氧酶-1而实现的。更多还原

【Abstract】 Objective: This study aimed to investigate the effects of probucol on the concentration and expression of paraoxonase-1 in hy-percholesterolemic rabbits and try to elucidate the antiatherogenic properties of probucol. Methods: Sixteen rabbits fed with high cholesterol diet for 8 weeks were randomly divided into two groups:①high cholesterol group (n = 8) : high cholesterol diet lasting for 6 weeks;②probucol group (n = 8) ; high cholesterol diet plus 1 % probucol for 6 weeks. Control group (n = 8) was fed with normal diet for 14 weeks. The classical in-situ two steps perfusion of the liver with collagenase IV was used to isolate the parenchymal hepatocytes. The total superoxide dismutase activity and malondialdehyde and paraoxonase 1 concentration in plasma were measured at 0, 8 and 14 weeks of feeding. Reverse transcription polymerase chain reaction ( RT-PCR) was used to detect mRNA expression of PON-1 in hepatocytes. The histopathological changes of aortas were determined at the end of the study. Results: Compared with those in control group, rabbits fed with high cholesterol diet showed higher levels of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL-C, all of which were significantly reduced by probucol treatment. The plaque areas (51. 54±8. 32% ) of the aorta were ameliorated in probucol group as compared with high cholesterol group (84. 81±9. 35% ). Probucol significantly decreased the MDA concentration(9. 20±1. 31μg/ml) as compared with high cholesterol group (12. 57±1. 43μg/ml, P <0. 01), but had no effect on SOD activity. Probucol significantly increased PON-1 content and up-regulated the mRNA expression of PON-1 as compared with high cholesterol group (0. 85±0. 02μg/ml vs 0. 50±0. 01μg/ml; 0. 72±0. 01 vs 0. 46±0. 01, respectively, all P < 0. 05). The PON-1 concentration was negatively associated with the MDA concentration ( r = - 0. 86, P = 0. 003) but not the level of HDL-C. Conclusions: Probucol decreased plasma lipid and MDA concentrations, and increased PON-1 concentration and its transcription in hepatocytes, which may contribute to its antiatherogenic effects.更多还原