Takeda Y, Arii S, Kaido T, Niwano M, Moriga T, Mori A, Hanaki K, Gorrin-Rivas M J, Ishii T, Sato M, Imamura M
Department of Surgery and Surgical Basic Science, Faculty of Medicine, Kyoto University, Japan.
Transplantation. 1999 Mar 27;67(6):820-8. doi: 10.1097/00007890-199903270-00007.
Fatty liver grafts are considered to be one of the main factors of primary nonfunctioning graft in transplantation. We investigated here, the hepatic damage during cold preservation in a rat fatty liver model by ultrastructural observation, and examined the effect of human recombinant hepatocyte growth factor (hrHGF) on amelioration of the cold-preserved graft condition.
Wistar rats were fed a choline-deficient diet (CDD) for 7 days. Livers were stored in cold University of Wisconsin (UW) solution for 0, 4, and 24 hr. We evaluated the ultrastructural alteration of the hepatocytes, sinusoidal architecture, and endothelial cells (SECs) by scanning and transmission electron microscopy. Ex vivo, we measured alanine aminotransferase (ALT) in first effluent as an index of hepatocyte injury and the hyaluronic uptake rate (HUR) as that of SEC damage. We injected hrHGF into rats fed CDD for 7 days through the portal vein and also added it to the UW solution to determine whether or not the agent ameliorated the hepatic damage in cold-preserved fatty livers.
In rats fed CDD for 7 days, the lesion occupied by fat deposits appeared to enlarge with the duration of cold preservation leading to the disarrangement of sinusoidal architecture. Furthermore, sinusoidal endothelial damage, in which gaps, blebs, microvilli, and sinusoid denudation were detected, appeared to be more severe in these livers than in the corresponding control livers. ALT significantly increased in the 4-hr cold-preserved livers of rats fed CDD for 7 days. HUR decreased with 4-hr cold preservation and/or with CDD feeding. Administration of hrHGF prevented the expansion of fatty droplets and reduced SEC injury as detected by morphological observations. Increase of ALT in first effluent was inhibited to about one fourth the level observed in the 4-hr cold-preserved livers of rats fed CDD. Moreover, HUR significantly increased with the pretreatment of hrHGF.
The hepatic injury in both hepatocytes and SECs in cold-preserved fatty liver graft developed more rapidly and severely than in the corresponding controls and demonstrated a protective effect of hrHGF.
脂肪肝移植物被认为是移植中原发性移植物无功能的主要因素之一。在此，我们通过超微结构观察研究大鼠脂肪肝模型冷保存期间的肝损伤，并检测重组人肝细胞生长因子（hrHGF）对改善冷保存移植物状况的作用。
将Wistar大鼠给予胆碱缺乏饮食（CDD）7天。肝脏在冷的威斯康星大学（UW）溶液中保存0、4和24小时。通过扫描和透射电子显微镜评估肝细胞、肝血窦结构和内皮细胞（SECs）的超微结构改变。在体外，我们测量首次流出液中的丙氨酸转氨酶（ALT）作为肝细胞损伤指标，测量透明质酸摄取率（HUR）作为SECs损伤指标。我们通过门静脉将hrHGF注射到给予CDD 7天的大鼠体内，并将其添加到UW溶液中，以确定该药物是否能改善冷保存脂肪肝的肝损伤。
在给予CDD 7天的大鼠中，脂肪沉积占据的病变似乎随着冷保存时间的延长而扩大，导致肝血窦结构紊乱。此外，在这些肝脏中检测到的肝血窦内皮损伤，包括间隙、泡状突起、微绒毛和肝血窦剥脱，似乎比相应的对照肝脏更严重。给予CDD 7天的大鼠冷保存4小时的肝脏中ALT显著升高。冷保存4小时和/或给予CDD后HUR降低。形态学观察显示，给予hrHGF可防止脂肪滴扩大并减少SECs损伤。首次流出液中ALT的升高被抑制到给予CDD的大鼠冷保存4小时肝脏中观察到水平的约四分之一。此外，hrHGF预处理后HUR显著升高。
冷保存脂肪肝移植物中肝细胞和SECs的肝损伤比相应对照发展得更快、更严重，并且证明了hrHGF的保护作用。
