Li J, Hirose N, Kawamura M, Arai Y
Department of Geriatrics Medicine, Keio University School of Medicine, Tokyo, Japan.
Atherosclerosis. 1999 Apr;143(2):315-26. doi: 10.1016/s0021-9150(98)00309-8.
The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.
本研究的目的是确定血管紧张素转换酶（ACE）抑制剂贝那普利和血管紧张素受体拮抗剂缬沙坦是否会降低喂饲胆固醇的家兔的动脉粥样硬化严重程度。雄性家兔被分为以下几组进行喂养：（a）正常兔粮；（b）2%胆固醇饮食；（c）2%胆固醇饮食并皮下注射贝那普利（每天3毫克/千克）；或（d）2%胆固醇饮食并皮下注射缬沙坦（每天1毫克/千克）。12周后，采集动脉进行组织形态计量学和免疫组织化学分析。我们观察到，与胆固醇组相比，贝那普利治疗组的血清甘油三酯（TG）、总胆固醇（TC）降低以及ACE活性降低分别超过60%、30%和84%；缬沙坦治疗组的TG水平比胆固醇组低53%，然而，TC和ACE活性无显著差异。与胆固醇组相比，贝那普利治疗组的主动脉表面动脉粥样硬化面积百分比、内膜厚度以及主动脉内膜面积与中膜面积之比降低约40%；在胸主动脉中差异超过60%。缬沙坦治疗组的动脉粥样硬化面积减少23%，效果不如贝那普利治疗。与胆固醇组相比，贝那普利治疗组的PCNA阳性细胞百分比和内膜增殖细胞数/平方毫米显著减少（分别减少55%和63%）；缬沙坦治疗组的这些参数分别降低35%和17%。胆固醇组中增殖巨噬细胞与平滑肌细胞（SMC）的比例为3:1，贝那普利治疗组为1:1，缬沙坦治疗组为2:1。这些结果表明，贝那普利可通过减少巨噬细胞在动脉壁中的增殖和积聚来降低动脉粥样硬化进展。贝那普利和缬沙坦降低动脉粥样硬化进展的机制可能与TG的降低和血管紧张素II作用的阻断有关。
