Kunitomo M, Takaoka K, Matsumoto J, Iwai H, Bando Y
Nihon Yakurigaku Zasshi. 1983 Apr;81(4):275-83.
Atherosclerotic lesions of aorta and arteries were induced in guinea pigs fed a diet supplemented with 1% cholesterol and vitamin D2 (0.75 million IU/kg of diet) for 6 weeks. Histopathological observation revealed intimal proliferation and calcification of the intima and media, but no atheroma was present at the sites of arterial injury. However, the biochemical findings revealed accumulation of cholesterol, mainly esterified, and calcium in the aorta. Significant correlation between the calcium and phosphorus contents in the aorta indicates the presence of a probable calcium-phosphate complex. Synergism for the induction of atherosclerotic lesions was shown between high cholesterol and excess vitamin D2. Sodium 4-(hexadecylamino)benzoate (cetaben) (90 mg/kg/day, p.o.) and trisodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) (5 mg/kg/day, s.c.) inhibited the development of atherosclerotic lesions induced in this manner. These effects were associated with a significant reduction of serum and aortic cholesterol levels and a significant elevation of HDL-cholesterol levels caused by cetaben, and a significant reduction in aortic calcium caused by EHDP. These two drugs and clofibrate, however, had no significant effect on the regression of pre-established atherosclerotic lesions.
给豚鼠喂食添加1%胆固醇和维生素D2(0.75百万国际单位/千克饲料)的饲料6周,诱导其主动脉和动脉出现动脉粥样硬化病变。组织病理学观察显示内膜增生以及内膜和中膜钙化,但在动脉损伤部位未出现动脉粥样瘤。然而,生化检查结果显示主动脉中胆固醇(主要是酯化胆固醇)和钙有所蓄积。主动脉中钙和磷含量之间存在显著相关性,表明可能存在磷酸钙复合物。高胆固醇和过量维生素D2之间显示出诱导动脉粥样硬化病变的协同作用。4-(十六烷基氨基)苯甲酸钠(西他苯)(90毫克/千克/天,口服)和乙烷-1-羟基-1,1-二膦酸三钠(EHDP)(5毫克/千克/天,皮下注射)抑制了以这种方式诱导的动脉粥样硬化病变的发展。这些作用与西他苯导致的血清和主动脉胆固醇水平显著降低以及高密度脂蛋白胆固醇水平显著升高,以及EHDP导致的主动脉钙显著减少有关。然而,这两种药物和氯贝丁酯对已形成的动脉粥样硬化病变的消退没有显著影响。