Finking G, Brehme U, Bruck B, Wehrmann M, Hanke S, Kamenz J, Kern S, Lenz C, Hanke H
Department of Internal Medicine, University of Ulm, Germany.
Vet Hum Toxicol. 1998 Jun;40(3):136-40.
The rabbit has been a widely accepted animal model for atherosclerosis research since Anitschkow first used this animal in 1913 in identifying dietary-induced hypercholesterolemia as a major risk factor for atherogenesis. Experiments with cholesterol-fed rabbits have demonstrated the beneficial effects of estrogen treatment on the development of atheroma for more than 50 y. Clinical trials have found a reduction in cardiovascular events of up to 50% in postmenopausal women receiving estrogen replacement therapy. However, metabolic conditions in rabbits, as well as physiological estrogen serum levels, differ in some aspects from those in humans. In rabbits, experimentally-induced hormone levels are about 5- to 10-fold higher than those found in untreated animals. Normal physiological estrogen levels in rabbits are not cardioprotective under dietary-induced hypercholesterolemia. We investigated whether replacement induced "hyperestrogenemia" causes adverse effects on organs other than the cardiovascular system. Twenty-nine female rabbits were divided into 4 different groups, 2 without and 2 with estrogen treatment (1 mg estradiol valerate/kg body weight/w over 12 w). Organ weights, transaminases and uterine histology were examined. In rabbits treated with estrogen, we did not see relevant adverse effects on heart, kidney and liver weights, or on liver enzymes. But there was a significant increase in spleen weights, as well as notable changes in the endometrium with moderate inflammation. These findings indicate that the dosage of estrogen commonly used for atherosclerosis research does not cause serious disorders in the major organs of cholesterol-fed rabbits.
自1913年阿尼奇科夫首次将兔子用于确定饮食诱导的高胆固醇血症是动脉粥样硬化发生的主要危险因素以来，兔子一直是动脉粥样硬化研究中广泛接受的动物模型。用高胆固醇饮食喂养兔子的实验已经证明雌激素治疗对动脉粥样硬化发展具有有益作用超过50年。临床试验发现接受雌激素替代疗法的绝经后女性心血管事件减少高达50%。然而，兔子的代谢状况以及生理血清雌激素水平在某些方面与人类不同。在兔子中，实验诱导的激素水平比未处理动物中发现的激素水平高约5至10倍。在饮食诱导的高胆固醇血症情况下，兔子正常的生理雌激素水平并无心脏保护作用。我们研究了替代诱导的“高雌激素血症”是否会对心血管系统以外的器官产生不利影响。将29只雌性兔子分为4组，2组不进行雌激素治疗，2组进行雌激素治疗（戊酸雌二醇1毫克/千克体重/周，共12周）。检查了器官重量、转氨酶和子宫组织学。在用雌激素治疗的兔子中，我们没有看到对心脏、肾脏和肝脏重量或肝酶有相关的不利影响。但是脾脏重量显著增加，子宫内膜也有明显变化并伴有中度炎症。这些发现表明，动脉粥样硬化研究中常用的雌激素剂量不会在高胆固醇饮食喂养的兔子的主要器官中引起严重紊乱。
