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低剂量雌激素可抑制绝经后猴子的冠状动脉粥样硬化。

Low dose estrogens inhibit coronary artery atherosclerosis in postmenopausal monkeys.

作者信息

Appt Susan E, Clarkson Thomas B, Lees Cynthia J, Anthony Mary S

机构信息

Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States.

出版信息

Maturitas. 2006 Sep 20;55(2):187-94. doi: 10.1016/j.maturitas.2006.02.002. Epub 2006 Mar 29.

Abstract

OBJECTIVES

To determine if low dose conjugated equine estrogens (CEE) result in a reduction of coronary artery atherosclerosis progression, and to relate these findings to previous studies using the traditional dose.

METHODS

Adult female monkeys (Macaca fascicularis) were fed an atherogenic diet for 10 months, to induce fatty streaks and small plaques comparable to those present in early postmenopausal women, and then ovariectomized and treated orally with: CEE (0.30 mg/day women's equivalent dose, n=28) or placebo (n=25) daily for 24 months. Body weight and estradiol were measured at 3, 6, 12 and 18 months and plasma lipids were measured at baseline and every 6 months.

RESULTS

Despite the lack of effect on plasma lipid profiles, monkeys treated with low dose CEE had marked reductions in coronary artery atherosclerosis plaque extent (intimal area) in all three main coronary arteries: left anterior descending artery (52% less, 0.044 mm(2) versus 0.091 mm(2), p=0.04); left circumflex artery (62% less, 0.045 mm(2) versus 0.119 mm(2), p=0.006) and right circumflex artery (42% less, 0.018 mm(2) versus 0.031 mm(2), p=0.20). The overall mean coronary atherosclerosis extent was 52% lower in CEE treated animals (0.042 mm(2) versus 0.088 mm(2), p=0.02).

CONCLUSION

Low dose CEE (0.30 mg/woman/day equivalent) was effective in reducing coronary atherosclerosis and the magnitude of the protection was comparable to previously reported studies using doses equivalent to 0.625 mg/woman/day. This study provides an experimental basis for the assumption that low dose CEE may be as effective as the traditional dose in inhibiting coronary atherosclerosis progression in early postmenopausal subjects.

摘要

目的

确定低剂量结合马雌激素(CEE)是否能降低冠状动脉粥样硬化进展,并将这些发现与之前使用传统剂量的研究相关联。

方法

成年雌性猕猴(食蟹猴)接受致动脉粥样化饮食10个月,以诱导出与绝经后早期女性中存在的脂肪条纹和小斑块相当的病变,然后进行卵巢切除术,并每日口服:CEE(0.30毫克/天女性等效剂量,n = 28)或安慰剂(n = 25),持续24个月。在3、6、12和18个月时测量体重和雌二醇,并在基线和每6个月时测量血脂。

结果

尽管对血脂谱没有影响,但接受低剂量CEE治疗的猕猴在所有三条主要冠状动脉中的冠状动脉粥样硬化斑块范围(内膜面积)均有显著减少:左前降支动脉(减少52%,0.044平方毫米对0.091平方毫米,p = 0.04);左旋支动脉(减少62%,0.045平方毫米对0.119平方毫米,p = 0.006)和右冠状动脉(减少42%,0.018平方毫米对0.031平方毫米,p = 0.20)。接受CEE治疗的动物的总体平均冠状动脉粥样硬化程度低52%(0.042平方毫米对0.088平方毫米,p = 0.02)。

结论

低剂量CEE(0.30毫克/女性/天等效剂量)可有效降低冠状动脉粥样硬化,保护程度与之前报道的使用0.625毫克/女性/天等效剂量的研究相当。本研究为低剂量CEE在抑制绝经后早期受试者冠状动脉粥样硬化进展方面可能与传统剂量同样有效的假设提供了实验依据。

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