Beitz J, Krüger J, Beitz A, Pawelski K, Szymanski C, Rath F W, Mest H J
Department of Pharmacology and Toxicology, Martin Luther University Halle-Wittenberg, FRG.
Biomed Biochim Acta. 1991;50(1):101-7.
Daily administration of the trapidil derivative AR 12463 (20 mg/kg body weight i.p.) to cholesterol-fed rabbits diminished statistically significantly the increase in serum total cholesterol. After 8 weeks of treatment all measured lipoprotein fractions were significantly lower in animals treated with AR 12463 (group 3) compared with the values of the untreated control (group 1) or vehicle-treated group (group 2). The reduction of serum levels was associated with statistically significantly reduced levels of cholesterol esters in kidney, liver and aorta. The levels of free cholesterol in the liver of group 3 animals were statistically significantly lower compared with the levels in the two other groups, whereas in kidney and aortas the levels of free cholesterol remained unchanged under the influence of AR 12463. The area of aorta covered with fatty streaks was significantly smaller in group 3 versus group 1. The results of this study indicate that treatment of rabbits with AR 12463 while feeding a cholesterol-rich diet prevents hypercholesterolemia as well as the cholesterol incorporation into tissues. The mode of action of AR 12463 on serum and tissue lipids as well as on the development of atherosclerosis is discussed.
给喂食胆固醇的兔子每日腹腔注射特拉匹定衍生物AR 12463（20毫克/千克体重），可使血清总胆固醇的升高在统计学上显著降低。治疗8周后，与未治疗的对照组（第1组）或赋形剂治疗组（第2组）相比，用AR 12463治疗的动物（第3组）中所有检测的脂蛋白组分均显著降低。血清水平的降低与肾脏、肝脏和主动脉中胆固醇酯水平在统计学上显著降低相关。第3组动物肝脏中的游离胆固醇水平与其他两组相比在统计学上显著降低，而在肾脏和主动脉中，在AR 12463的影响下，游离胆固醇水平保持不变。与第1组相比，第3组中覆盖有脂肪条纹的主动脉面积显著更小。本研究结果表明，在喂食富含胆固醇的饮食时用AR 12463治疗兔子可预防高胆固醇血症以及胆固醇在组织中的沉积。本文讨论了AR 12463对血清和组织脂质以及动脉粥样硬化发展的作用方式。
