REGRESSION OF ATHEROSCLEROSIS IN FEMALE MONKEYS
REGRESSION OF ATHEROSCLEROSIS IN FEMALE MONKEYS
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DOI：
10.1161/01.atv.15.7.827
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发表时间：
1995-07-01
影响因子：
8.7
通讯作者：
CLARKSON, TB
中科院分区：
文献类型：
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作者：
WILLIAMS, JK;ANTHONY, MS;CLARKSON, TB
本研究的目的是确定经手术治疗的绝经后患有冠状动脉粥样硬化的猴子在降低血脂和激素替代后动脉壁发生的结构和功能变化。88只手术绝经后食蟹猴喂食致动脉粥样硬化饮食24个月，然后分为4组：1组（n=20），基线尸检组；第2组（n=25），仅采用降脂饮食；第3组（n=22），降脂加马结合雌激素治疗相当于女性0.625 mg/d；第4组（n=21），降脂加结合马雌激素和醋酸甲孕酮治疗（相当于女性2.5 mg/d）。治疗30个月。灌注固定冠状动脉的组织形态学分析显示，与1组相比，各组斑块大小均无显著变化（P < 0.05）。血脂降低允许冠状动脉重构发生（冠状动脉和管腔大小比1组增加一倍）（P.4），但添加醋酸甲孕酮降低了结合雌激素对冠状动脉血流储备的有益作用（P=.03）。综上所述，雌性猴子降脂的主要动脉后遗症是动脉和管腔扩大，以及心外膜大冠状动脉的反应性改善。除了冠状动脉微循环的扩张能力外，在饮食调整中加入激素替代并没有进一步增强这些改善。
The objective of this study was to determine the structural and functional changes that occur in the artery wall in response to plasma lipid lowering and hormone replacement in surgically postmenopausal monkeys with established coronary artery atherosclerosis. Eighty-eight surgically postmenopausal cynomolgus monkeys were fed an atherogenic diet for 24 months and were then allocated into 4 groups: group 1 (n=20), a baseline necropsy group; group 2 (n=25), a lipid-lowering diet only; group 3 (n=22), lipid lowering plus conjugated equine estrogen treatment equivalent to 0.625 mg/d for a woman; and group 4 (n=21), lipid lowering plus conjugated equine estrogen and medroxyprogesterone acetate treatment (equivalent to 2.5 mg/d for a woman). Treatment was for 30 months. Histomorphometric analysis of perfusion-fixed coronary arteries revealed that plaque size did not change significantly in any of the groups compared with group 1 (P>.20). Plasma lipid lowering permitted coronary artery remodeling to occur (coronary artery and lumen size doubled compared with group 1) (P.4), but addition of medroxyprogesterone acetate diminished the beneficial effects of conjugated estrogens on coronary flow reserve (P=.03). In summary, the major arterial sequelae of lipid lowering in female monkeys were artery and lumen enlargement and improved reactivity of large epicardial coronary arteries. Addition of hormone replacement to the dietary modification did not further augment these improvements, except for the dilator capacity of the coronary microcirculation.