Korczyńska J, Stelmańska E, Nieweglowski T, Szołkiewicz M, Rutkowski B, Swierczyński J
Department of Biochemistry, Medical University of Gdańsk, Poland.
Pol J Pharmacol. 2000 Jul-Aug;52(4):291-7.
Fibrates have been used clinically to treat dyslipidemias, including chronic renal failure (CRF)-related hypertriacylgliceridemia. In addition to their effects on plasma triacylglycerol concentration, fibrates also induce hepatomegaly (due to peroxisome proliferation) and increase liver malic enzyme activity. Since most experiments regarding fibrates action have been performed on healthy animals, in this paper we compare the effect of clofibrate on: a) plasma lipid concentration; b) liver weight; c) liver malic enzyme gene expression (malic enzyme activity, malic enzyme protein level and malic enzyme mRNA abundance) in control (sham-operated) animals and rats with CRF. The data presented in this paper indicate that: a) the clofibrate treatment causes a decrease in triacylglycerol concentration both in the control and rats with CRF, however the effect of the drug was more pronounced in the latter; b) administration of clofibrate induces hepatomegaly both in the control and rats with CRF; c) the liver malic enzyme gene expression is similarly affected by clofibrate in the control and rats with CRF. It is concluded that the beneficial, therapeutic effect of clofibrate on plasma lipid concentration is more pronounced in rats with CRF, but the side effects (hepatomegaly and the increase in malic enzyme gene expression) of fibrates are essentially similar in the control and rats with CRF.
贝特类药物已被临床用于治疗血脂异常，包括与慢性肾衰竭（CRF）相关的高甘油三酯血症。除了对血浆甘油三酯浓度的影响外，贝特类药物还会引起肝肿大（由于过氧化物酶体增殖）并增加肝脏苹果酸酶活性。由于大多数关于贝特类药物作用的实验是在健康动物身上进行的，因此在本文中，我们比较了氯贝丁酯对以下方面的影响：a）血浆脂质浓度；b）肝脏重量；c）对照（假手术）动物和CRF大鼠的肝脏苹果酸酶基因表达（苹果酸酶活性、苹果酸酶蛋白水平和苹果酸酶mRNA丰度）。本文提供的数据表明：a）氯贝丁酯治疗使对照动物和CRF大鼠的甘油三酯浓度均降低，然而该药物在后者中的作用更为明显；b）给予氯贝丁酯会使对照动物和CRF大鼠均出现肝肿大；c）氯贝丁酯对对照动物和CRF大鼠肝脏苹果酸酶基因表达的影响相似。得出的结论是，氯贝丁酯对血浆脂质浓度的有益治疗作用在CRF大鼠中更为明显，但贝特类药物的副作用（肝肿大和苹果酸酶基因表达增加）在对照动物和CRF大鼠中基本相似。
