Shiomi M, Ito T, Watanabe Y, Tsujita Y, Kuroda M, Arai M, Fukami M, Fukushige J, Tamura A
Institute for Experimental Animals, Kobe University School of Medicine, Japan.
Atherosclerosis. 1990 Jul;83(1):69-80. doi: 10.1016/0021-9150(90)90132-3.
We investigated the possibility that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed or even regressed when their serum cholesterol levels were kept extremely low. Ten-month-old WHHL rabbits were divided into 3 groups, i.e. control rabbits, sacrificed at age 10 months, and placebo and treated rabbits, sacrificed at age 18 months. The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks. The serum cholesterol levels and atherogenic lipoproteins in the treated group were markedly reduced, by about 60% (P less than 0.005 and P less than 0.001). Consequently, the degrees of both coronary and aortic atherosclerosis in the treated group were significantly reduced compared with the placebo group, and were almost the same as in the control group. The histopathological findings supported the above results. In addition, the incidence and degree of xanthomas in digital joints in the treated group were significantly reduced. These results suggest that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed by keeping their serum cholesterol levels extremely low by the combination drug treatment.
我们研究了一种可能性，即当成熟的WHHL兔的血清胆固醇水平保持极低时，其已形成的动脉粥样硬化和黄色瘤可能会受到抑制甚至消退。将10月龄的WHHL兔分为3组，即10月龄时处死的对照兔，以及18月龄时处死的安慰剂组和治疗组兔。治疗组兔给予普伐他汀钠（50毫克/千克/天），一种HMG-CoA还原酶抑制剂，与消胆胺（饮食中2%），一种胆汁酸螯合剂，联合使用36周。治疗组的血清胆固醇水平和致动脉粥样硬化脂蛋白显著降低，降低约60%（P<0.005和P<0.001）。因此，与安慰剂组相比，治疗组的冠状动脉和主动脉粥样硬化程度均显著降低，且几乎与对照组相同。组织病理学结果支持上述结果。此外，治疗组手指关节黄色瘤的发生率和程度显著降低。这些结果表明，通过联合药物治疗使成熟的WHHL兔的血清胆固醇水平保持极低，可以抑制其已形成的动脉粥样硬化和黄色瘤。
