Recent studies have shown that endothelial function is impaired in patients with coronary artery disease (CAD). Probucol has been recognized to have antioxidant properties as well as lipid-lowering effects, and may improve endothelial function. The aim of this study was to evaluate the effects of probucol on endothelial function in patients with CAD. We evaluated endothelial function, based on flow-mediated vasodilation during reactive hyperemia (FMD), and the intima-media thickness (IMT) of the common carotid artery using high resolution ultrasonography in patients either with (CAD group, n=26) or without CAD (Control group, n=12). We measured the serum cholesterol concentration, including the low-density lipoprotein cholesterol (LDL-cholesterol) concentration, and the plasma concentrations of homocyst(e)ine and asymmetric dimethylarginine (ADMA). Measurements of FMD and serum cholesterol were repeated after 3 months of probucol (500 mg/day, n=9) or placebo (n=9) treatment in patients with CAD. The IMT was significantly greater (p < 0.001) and FMD was significantly lower (p < 0.001) in the CAD group than in the Control group. While the serum cholesterol concentration and plasma ADMA were similar in the two groups, the plasma homocyst(e)ine concentrations were higher in the CAD group than in the Control group (p < 0.01). After probucol therapy, FMD was significantly improved in the CAD group (p < 0.05). The serum LDL-cholesterol concentration did not significantly decrease after probucol treatment. Placebo treatment did not alter FMD or the serum cholesterol concentration. Our findings suggest that long-term treatment with probucol improves endothelial function in patients with CAD, an outcome independent of the LDL-cholesterol-lowering effects of probucol, and that homocyst(e)ine may be a better predictor of atherosclerosis than ADMA.
最近的研究显示，冠心病（CAD）患者内皮功能受损。普罗布考除降脂作用外，还有抗氧化作用，可提高内皮功能。该研究目的是评价普罗布考对冠心病患者内皮功能的影响。我们通过反应性充血（FMD）时血流介导的血管舒张评价内皮功能，并用超声评价颈动脉中膜厚度（IMT），冠心病组16例，无冠心病组12例。我们测定了血清胆固醇浓度，包括LDL-C浓度、血清同型半胱氨酸浓度和非对称二甲基精氨酸浓度 (ADMA)。普罗布考和安慰剂治疗3个月后重复测定FMD和胆固醇。冠心病组IMT明显升高 (p < 0.001)，FMD明显降低 (p < 0.001)。血浆胆固醇浓度和血浆ADMA在两组相似，同型半胱氨酸浓度冠心病组高于对照组(p < 0.05)。安慰剂治疗没有改变FMD或血清胆固醇浓度。我们的结果提示，长期的普罗布考治疗可提高冠心病患者内皮功能，这种作用独立于降低LDL-C的作用，同型半胱氨酸是比ADMA更好的动脉粥样硬化预测因子。 |
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