Staels B, van Tol A, Chan L, Verhoeven G, Auwerx J
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Gasthuisberg, Belgium.
Arterioscler Thromb. 1991 May-Jun;11(3):760-9. doi: 10.1161/01.atv.11.3.760.
Treatment of male rats with hydrocortisone provoked a dose- and time-dependent decrease in plasma cholesterol concentration without a change in plasma triglyceride levels. In contrast, administration of triamcinolone and dexamethasone at equipotent glucocorticoid doses increased plasma cholesterol and triglyceride levels, respectively. Small effects on apolipoprotein E (apo E) and apo B mRNA levels were observed, but all corticosteroids increased apo A-I and apo A-IV mRNA and decreased apo A-II mRNA levels in the liver. Triamcinolone and dexamethasone, however, were three times more potent in stimulating hepatic apo A-IV gene expression than was hydrocortisone, whereas liver apo A-I and apo A-II mRNA levels were altered to a similar extent by all corticosteroids. Plasma apo A-I and apo B concentrations always varied in a similar fashion with their respective liver mRNA levels after administration of the distinct corticoids. For apo A-IV and apo E, discrepancies between plasma and liver mRNA levels after administration of the different steroids, however, point to additional regulatory effects on plasma apolipoprotein levels. We conclude that 1) in contrast to plasma apo A-I and apo B, alterations in plasma lipid, apo A-IV, and apo E levels depend on the type of corticosteroid used; and 2) glucocorticoids have a differential effect on hepatic mRNA levels of apo A-I and apo A-IV on the one hand and apo A-II on the other hand, an effect that may be of consequence in the process of reverse cholesterol transport.
用氢化可的松处理雄性大鼠会导致血浆胆固醇浓度呈剂量和时间依赖性降低,而血浆甘油三酯水平无变化。相比之下,以等效糖皮质激素剂量给予曲安西龙和地塞米松,分别会增加血浆胆固醇和甘油三酯水平。观察到对载脂蛋白E(apo E)和apo B mRNA水平有微小影响,但所有皮质类固醇都会增加肝脏中apo A-I和apo A-IV mRNA水平,并降低apo A-II mRNA水平。然而,曲安西龙和地塞米松刺激肝脏apo A-IV基因表达的效力是氢化可的松的三倍,而所有皮质类固醇对肝脏apo A-I和apo A-II mRNA水平的改变程度相似。给予不同皮质类固醇后,血浆apo A-I和apo B浓度总是与其各自肝脏mRNA水平以相似方式变化。然而,对于apo A-IV和apo E,给予不同类固醇后血浆和肝脏mRNA水平之间的差异表明对血浆载脂蛋白水平有额外的调节作用。我们得出结论:1)与血浆apo A-I和apo B不同,血浆脂质、apo A-IV和apo E水平的改变取决于所用皮质类固醇的类型;2)糖皮质激素对肝脏中apo A-I和apo A-IV的mRNA水平以及apo A-II的mRNA水平有不同影响,这种影响可能在逆向胆固醇转运过程中具有重要意义。