Hollander W, Paddock J, Nagraj S, Colombo M, Kirkpatrick B
Atherosclerosis. 1979 May;33(1):111-23. doi: 10.1016/0021-9150(79)90202-8.
The effects of the anticalcifying drug, ethane-hydroxydiphosphonate (EHDP) and the inhibitors of collagen biosynthesis, colchicine, penicillamine and azetidine were studied in the rabbit with pre-established atherosclerosis. The drugs were administered with a cholesterol-free diet (regression diet) for 8 weeks following the induction of atherosclerosis by feeding a hypercholesterolemic diet containing 2% cholesterol and 8% peanut oil for 8 weeks. The extent and severity of aortic atherosclerosis, as revealed by the morphological and biochemical findings, increased significantly during the regression period. In rabbits treated with EHDP (5 mg/kg/day) the aorta had fewer gross lesions and contained significantly less cholesterol, collagen and elastin than did the aorta of the rabbits fed the regression diet alone. These changes were associated with a significant reduction in aortic calcium caused by EHDP. The aortic content of cholesterol, collagen and elastin in the EHDP-treated rabbits, although less than that of the rabbits fed the regression diet alone, was about the same as that of the rabbits fed a high cholesterol diet for 8 weeks. Both colchicine (0.2 mg/kg/day) and penicillamine (100 mg/kg/day) had a selective action on the induced plaques in that they suppressed the fibrous proliferation in the lesions without preventing lipid and calcium accumulation in the lesions. Neither colchicine nor penicillamine reduced the extent of aortic atherosclerosis as determined by gross examination of the vessel. Azetidine had no significant effect on the pre-established atherosclerotic lesions. The lipid, fibrous protein and calcium content of the aorta of the azetidine-treated animals was not significantly different from that of the untreated animals. The biochemical findings in the aorta were consistent with the microscopic changes.
在预先患有动脉粥样硬化的兔子身上，研究了抗钙化药物乙烷羟基二膦酸盐（EHDP）以及胶原蛋白生物合成抑制剂秋水仙碱、青霉胺和氮杂环丁烷的作用。在用含2%胆固醇和8%花生油的高胆固醇饮食喂养8周诱导动脉粥样硬化后，给予这些药物并搭配无胆固醇饮食（消退饮食）持续8周。从形态学和生化检查结果来看，在消退期主动脉粥样硬化的范围和严重程度显著增加。用EHDP（5毫克/千克/天）治疗的兔子，其主动脉肉眼可见的病变较少，胆固醇、胶原蛋白和弹性蛋白的含量明显低于仅喂食消退饮食的兔子。这些变化与EHDP导致的主动脉钙含量显著降低有关。经EHDP治疗的兔子主动脉中胆固醇、胶原蛋白和弹性蛋白的含量，虽然低于仅喂食消退饮食的兔子，但与喂食高胆固醇饮食8周的兔子大致相同。秋水仙碱（0.2毫克/千克/天）和青霉胺（100毫克/千克/天）对诱导形成的斑块有选择性作用，即它们抑制病变中的纤维增生，但不阻止病变中脂质和钙的积累。通过对血管的大体检查确定，秋水仙碱和青霉胺均未降低主动脉粥样硬化的程度。氮杂环丁烷对预先形成的动脉粥样硬化病变没有显著影响。氮杂环丁烷处理组动物主动脉的脂质、纤维蛋白和钙含量与未处理组动物没有显著差异。主动脉的生化检查结果与微观变化一致。
