Wagenaar G T, Chamuleau R A, Pool C W, de Haan J G, Maas M A, Korfage H A, Lamers W H
Department of Anatomy and Embryology, University of Amsterdam, The Netherlands.
J Hepatol. 1993 Mar;17(3):397-407. doi: 10.1016/s0168-8278(05)80224-7.
Glutamine synthase and carbamoylphosphate synthase show a strikingly heterogeneous and fully complementary distribution in the rat liver. In the human liver, however, there is a midlobular zone where both enzymes are absent. The diameter of the human liver lobule is approximately twice the size of the rat lobule. To investigate whether lobule size is a major determinant for the expression patterns of glutamine synthase and carbamoylphosphate synthase, Wistar strain rats were partially hepatectomized 3 times, at weekly or monthly intervals. Due to hepatic regeneration the cross-sectional area of the liver lobules increased twofold. However, a midlobular zone which lacked expression of both glutamine synthase and carbamoylphosphate synthase did not develop in these livers, thus showing that lobular size is not a major determinant for the distribution patterns of glutamine and carbamoylphosphate synthase. The twofold increase in the cross-sectional area of the liver lobule was associated with a similar reduction in the relative number of glutamine synthase-positive cells and in the enzyme content of the liver, indicating that the regeneration process does not affect the pericentral pattern of glutamine synthase expression. After regeneration was complete, the glutamine synthase content in the liver was restored to its original value, demonstrating a twofold increase in the cellular concentration of glutamine synthase-positive hepatocytes. An increase in the diameter of the liver lobule was only seen after the first partial hepatectomy. Liver growth following subsequent partial hepatectomies can be explained by an increase in the length of the liver lobule and/or by splitting of liver lobules. The zonal distribution of DNA replication, which is characteristic of the first partial hepatectomy, is lost after repeated partial hepatectomies. Furthermore, evidence was obtained that the signal for inducing DNA synthesis may originate at the level of single liver units.
谷氨酰胺合成酶和氨甲酰磷酸合成酶在大鼠肝脏中呈现出显著的异质性和完全互补的分布。然而，在人类肝脏中，存在一个中央小叶区，这两种酶在该区域均不存在。人类肝小叶的直径约为大鼠肝小叶的两倍。为了研究小叶大小是否是谷氨酰胺合成酶和氨甲酰磷酸合成酶表达模式的主要决定因素，对Wistar品系大鼠进行了3次部分肝切除术，间隔为每周或每月一次。由于肝脏再生，肝小叶的横截面积增加了两倍。然而，在这些肝脏中并未形成缺乏谷氨酰胺合成酶和氨甲酰磷酸合成酶表达的中央小叶区，这表明小叶大小不是谷氨酰胺和氨甲酰磷酸合成酶分布模式的主要决定因素。肝小叶横截面积增加两倍与谷氨酰胺合成酶阳性细胞的相对数量及肝脏中该酶含量的类似减少相关，这表明再生过程不影响谷氨酰胺合成酶表达的中央周围模式。再生完成后，肝脏中的谷氨酰胺合成酶含量恢复到其原始值，这表明谷氨酰胺合成酶阳性肝细胞的细胞浓度增加了两倍。仅在第一次部分肝切除术后观察到肝小叶直径增加。后续部分肝切除术后肝脏的生长可通过肝小叶长度的增加和/或肝小叶的分裂来解释。第一次部分肝切除所特有的DNA复制的区域分布在重复部分肝切除术后消失。此外，有证据表明诱导DNA合成的信号可能起源于单个肝单位水平。
