Pill J, Wolff S, Stegmeier K, Schmidt F H
Medizinische Forschung, Boehringer Mannheim GmbH, Mannheim, Germany.
Methods Find Exp Clin Pharmacol. 1988 Aug;10(8):487-92.
Rats, due to their availability and ease of handling, are a frequently used animal model for studying the effects of drugs on lipid metabolism. Hypolipidemic effects showed great variations in different studies. We investigated the effect of bezafibrate on serum concentrations of cholesterol and triglycerides in different strains of rats from several breeders. Under these conditions Lewis rats seemed to be the most suitable strain to investigate drug effects on cholesterol in serum. A hypercholesterolemic male Lewis rat found in a screening program was mated with normolipidemic female Lewis rats. The hyperlipidemia was found in some of the male and female offspring. Cholesterol and triglycerides were dramatically elevated in older animals. Bezafibrate (75 mg/kg/d) produced a marked reduction of lipids in serum in normo- and hyperlipidemic male rats but only in hyperlipidemic female rats, which is in agreement with former findings. These spontaneously hyperlipidemic rats could be a useful tool for investigation of drug effects on disturbed lipid metabolism and its pathophysiology. Therefore, we tried to establish a hyperlipidemic strain of rats.
由于大鼠容易获得且易于处理，它们是研究药物对脂质代谢影响时常用的动物模型。不同研究中降血脂作用表现出很大差异。我们研究了苯扎贝特对来自多个繁育者的不同品系大鼠血清胆固醇和甘油三酯浓度的影响。在这些条件下，Lewis大鼠似乎是研究药物对血清胆固醇影响的最合适品系。在一项筛选计划中发现的一只高胆固醇血症雄性Lewis大鼠与血脂正常的雌性Lewis大鼠交配。在一些雄性和雌性后代中发现了高脂血症。老年动物的胆固醇和甘油三酯显著升高。苯扎贝特（75毫克/千克/天）使正常血脂和高脂血症雄性大鼠的血清脂质显著降低，但仅使高脂血症雌性大鼠的血清脂质降低，这与之前的研究结果一致。这些自发性高脂血症大鼠可能是研究药物对紊乱脂质代谢及其病理生理学影响的有用工具。因此，我们试图建立一个高脂血症大鼠品系。
