Beaumont J L, Jacotot B, Buxtorf J C, Silvestre M, Beaumont V
Artery. 1982;10(1):71-87.
500 mg of probucol were given twice a day for 6 months to 20 type II hyperlipoproteinemic patients, 14 men and 6 women, including 10 type IIb and 10 type IIa cases. Tendon xanthomas were present in 11 and xanthelasma in 4. Their mean blood cholesterol level was 435 +/- 100 mg/100 ml and triglycerides 210 +/- 138 mg/100 ml. A normal diet was maintained during the treatment period. Skin biopsies were made on the forearm, before and after the 6 month treatment. After lyophilization of the skin fragments, the free and esterified cholesterol contents were measured by gas chromatography after preparative thin layer chromatography on silica gel. The free and esterified cholesterol contents of the skin both appear to be significantly increased when the values found before treatment in these patients are compared with those of skin analysis in 10 normal controls: 2.25 to 1.58 micrograms/mg freeze-dried skin, p less than 0.001 for the esterified fraction. After 6 month probucol treatment the free cholesterol does not change significantly (2.25 to 2.16) and the esterified cholesterol increases (0.44 to 0.66, p less than 0.01). This effect is suggestive of an interaction of probucol with the synthesis and transport of cholesterol at the tissue level. It may be significant for the understanding of the effects of this drug and others on xanthelasma, tendon xanthomas, and atherosclerosis. In one of the cases studied here, the xanthelasma was greatly reduced during the treatment.
对20例II型高脂蛋白血症患者（14名男性和6名女性，包括10例IIb型和10例IIa型病例）给予普罗布考，剂量为500毫克，每日2次，共6个月。11例患者有肌腱黄色瘤，4例有睑黄瘤。他们的平均血胆固醇水平为435±100毫克/100毫升，甘油三酯为210±138毫克/100毫升。治疗期间维持正常饮食。在6个月治疗前后，在前臂取皮肤活检。皮肤碎片冻干后，在硅胶上进行制备性薄层色谱分离，然后用气相色谱法测定游离胆固醇和胆固醇酯含量。将这些患者治疗前的皮肤分析值与10名正常对照者的皮肤分析值相比，皮肤中的游离胆固醇和胆固醇酯含量均显著增加：冻干皮肤中为2.25至1.58微克/毫克，胆固醇酯部分p<0.001。普罗布考治疗6个月后，游离胆固醇无显著变化（2.25至2.16），胆固醇酯增加（0.44至0.66，p<0.01）。这种效应提示普罗布考在组织水平上与胆固醇的合成和转运存在相互作用。这对于理解该药物及其他药物对睑黄瘤、肌腱黄色瘤和动脉粥样硬化的作用可能具有重要意义。在此研究的其中1例病例中，治疗期间睑黄瘤明显减轻。
