Racine-Samson L, Scoazec J Y, D'Errico A, Fiorentino M, Christa L, Moreau A, Roda C, Grigioni W F, Feldman G
Laboratoire de Biologie Cellulaire and Unité INSERM, Faculté de Medecine Xavier Bichat, Université Denis Diderot, Paris, France.
Hepatology. 1996 Jul;24(1):104-13. doi: 10.1002/hep.510240118.
Little is known about the alterations of metabolic organization of the human liver tissue in chronic liver diseases. We therefore compared the distribution of the following zonal metabolic markers in 10 samples of normal liver tissue, 10 samples of fibrotic tissue, and 22 samples of cirrhotic tissue: (a) the enzymatic activities of glucose-6-phosphatase (G6P), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), nicotinamide-adenine-dinucleotide-phosphate [NAPH] dehydrogenase (ND), beta-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine synthetase (GLS); and (c) albumin messenger RNA (mRNA). The normal human hepatic lobule was characterized by the periportal predominance of G6P and SDH enzymatic activities and albumin mRNAs, the perivenous predominance of ND and GDH, the restriction of GLS to a small perivenous compartment, and the predominanc of beta-HBDH at the contact of both portal tracts and centrilobular veins. In fibrosis, the overall metabolic organization of the normal liver tissue was retained. The expression of periportal markers predominated around enlarged portal tracts and that of perivenous markers around residual centrilobular veins. GLS was constantly detected at the contact of centrilobular veins. In cirrhotic nodules, no zonation was observed for most enzymatic activities or for albumin. Only G6P usually predominated at the periphery of the nodules. GLS was constantly undetectable. No difference accordingly to the etiology of the underlying disease was observed. In conclusion, the normal human hepatic lobule presents a marked metabolic zonation, preserved in fibrotic lesions, but lost in cirrhotic nodules. The alterations of the metabolic organization observed in cirrhosis might contribute to the pathogenesis of some of the metabolic disorders associated with advanced liver disease.
关于慢性肝病中人类肝组织代谢组织的改变，我们所知甚少。因此，我们比较了10份正常肝组织样本、10份纤维化组织样本和22份肝硬化组织样本中以下区域代谢标志物的分布情况：(a) 葡萄糖-6-磷酸酶（G6P）、乳酸脱氢酶（LDH）、琥珀酸脱氢酶（SDH）、烟酰胺腺嘌呤二核苷酸磷酸[NAPH]脱氢酶（ND）、β-羟基丁酸脱氢酶（HBDH）和谷氨酸脱氢酶（GDH）的酶活性；(b) 蛋白质谷氨酰胺合成酶（GLS）；(c) 白蛋白信使核糖核酸（mRNA）。正常人类肝小叶的特征是，G6P和SDH酶活性以及白蛋白mRNA在门静脉周围占优势，ND和GDH在肝静脉周围占优势，GLS局限于小的肝静脉周围区域，β-HBDH在门静脉和中央静脉的交界处占优势。在纤维化过程中，正常肝组织的整体代谢组织得以保留。门静脉周围标志物的表达在扩大的门静脉周围占主导，肝静脉周围标志物的表达在残留的中央静脉周围占主导。在中央静脉的交界处经常检测到GLS。在肝硬化结节中，大多数酶活性或白蛋白均未观察到分区现象。只有G6P通常在结节周边占优势。始终检测不到GLS。未观察到与潜在疾病病因相关的差异。总之，正常人类肝小叶呈现出明显的代谢分区，在纤维化病变中得以保留，但在肝硬化结节中消失。肝硬化中观察到的代谢组织改变可能有助于某些与晚期肝病相关的代谢紊乱的发病机制。
