Massey E D, Butler W H
Chem Biol Interact. 1979 Mar;24(3):329-44. doi: 10.1016/0009-2797(79)90081-4.
Alterations in the liver of rats subjected to 24 days of continuous administration of phenobarbitone have been supplied bu subcellular fractionation, conventional electron microscopy and morphometric analysis. The increase in wet weight of the liver was found to result from a combination of cellular hypertrophy, hyperplasia and an enlarged hepatic blood space. In the centrilobular zone all the hepatocytes underwent a substantial proliferation of total ER, became enlarged and had an increased blood supply. However, in the periportal zone phenobarbitone caused changes in only 45% of the hepatocytes, the remainder being apparently resistent or tardy. An overall dramatic increase in hepatic RER was both measured and observed but the response involved hepatocytes in which the RER had proliferated as well as those which were depleted of RER or had stacks and cisternae that were severely shortened and dispersed. These alterations are discussed in relation to changes in RER after administration of agents causing hepatonecrosis. Possible reasons for the inability of other workers to detect a phenobarbitone-induced increase in RER are also put forward. After subcellular fractionation and corection for centrifugation losses into the 9500 g pellet, using the microsomal marker cytochrome P-450, phenobarbitone-induced increase in total ER was substantially less than that found by morphometric analysis. This indicates that during the preparation of microsomes a substantial proportion of intracellular membranes, having different metabolic and synthetic properties to those finally isolated, are discarded and emphasizes the need to exercise care when using microsomal preparations.
通过亚细胞分级分离、传统电子显微镜检查和形态计量分析，对连续24天给予苯巴比妥的大鼠肝脏变化进行了研究。发现肝脏湿重增加是细胞肥大、增生和肝血窦扩大共同作用的结果。在小叶中心区，所有肝细胞的内质网总量均大量增殖，细胞体积增大，血供增加。然而，在汇管区周围，苯巴比妥仅使45%的肝细胞发生变化，其余肝细胞显然具有抗性或反应迟缓。通过测量和观察均发现肝脏粗面内质网总体显著增加，但这种反应涉及内质网增殖的肝细胞以及内质网减少或内质网堆叠和潴泡严重缩短且分散的肝细胞。结合给予导致肝坏死的药物后粗面内质网的变化对这些改变进行了讨论。还提出了其他研究人员未能检测到苯巴比妥诱导的粗面内质网增加的可能原因。在进行亚细胞分级分离并使用微粒体标记细胞色素P - 450校正9500g沉淀中的离心损失后，发现苯巴比妥诱导的内质网总量增加明显低于形态计量分析结果。这表明在微粒体制备过程中，很大一部分具有与最终分离的内膜不同代谢和合成特性的细胞内膜被丢弃，强调了使用微粒体制备时需谨慎的必要性。
