Schmucker D L, Jones A L
J Lipid Res. 1975 Mar;16(2):143-50.
Hepatic fine structural alterations induced by shortterm administration of the hypolipidemic drug oxandrolone were evaluated using morphometric techniques. These changes are described in the livers of normolipidemic young adult and hyperlipidemic retired breeder male rats. Retired breeder rats, characterized by hyperlipidemia and a high incidence of arteriosclerosis, are thought to undergo premature aging. A previous morphometric study has shown that the hepatocytes of retired breeder rats are larger, contain a greater volume fraction of lysosomes, and have significantly less smooth-surfaced endoplasmic reticulum than those of young adult rats. However, after oxandrolone administration, the livers of these two animal groups were no longer distinguishable on the basis of these morphometric parameters. Unlike a number of other hypolipidemic drugs, oxandrolone does not induce a marked proliferation of hepatic microbodies. The effect of oxandrolone on the livers of prematurely aging rats suggests that the age-related fine structural changes are not the result of irreversible alterations in the genome or translation-transcription apparatus but may actually represent secondary reactions to extrahepatic and/or endocrine metabolic changes. The relationship between (1) aging and hyperlipidemia and (2) aging and the reduced hepatic capacity to metabolize drugs suggest a need to evaluate the effects of lipid-lowering drugs on the livers of old as well as young animal models.
运用形态计量学技术评估了短期给予降血脂药物氧雄龙所诱导的肝脏细微结构改变。这些变化在血脂正常的年轻成年雄性大鼠和高脂血症的退休种鼠的肝脏中进行了描述。退休种鼠以高脂血症和高动脉硬化发生率为特征，被认为会过早衰老。先前的形态计量学研究表明，退休种鼠的肝细胞更大，溶酶体的体积分数更高，并且与年轻成年大鼠相比，其光滑表面内质网显著更少。然而，给予氧雄龙后，这两组动物的肝脏在这些形态计量学参数上不再有差异。与许多其他降血脂药物不同，氧雄龙不会诱导肝脏微体显著增殖。氧雄龙对过早衰老大鼠肝脏的影响表明，与年龄相关的细微结构变化不是基因组或翻译转录装置不可逆改变的结果，而实际上可能代表对肝外和/或内分泌代谢变化的继发反应。（1）衰老与高脂血症以及（2）衰老与肝脏药物代谢能力降低之间的关系表明，有必要评估降脂药物对老年和年轻动物模型肝脏的影响。
