Takeda Yoshihisa, Arii Shigeki, Kaido Toshimi, Imamura Masayuki
Department of Surgery, Hikone City Hospital, 1882 Hassaka-cho Hikone, 522-8539, Shiga, Japan.
Transpl Int. 2003 Apr;16(4):241-9. doi: 10.1007/s00147-003-0548-8. Epub 2003 Feb 26.
A fatty liver resulting from alcohol intake is often unattractive for grafting. In this study, we investigated the impairment of hepatocytes and sinusoidal endothelial cells (SECs) during cold preservation of alcohol-induced fatty liver and examined the efficacy of human recombinant hepatocyte growth factor (hrHGF). Rats were fed an alcohol diet. We performed histological examinations of the hepatocytes and observed the ultrastructural alteration of the SECs. Additionally, we measured hepatic transaminase and peroxidative lipids for hepatocellular injury and the hyaluronic acid uptake rate (HUR) to determine SEC injury. We added hrHGF to University of Wisconsin (UW) solution to assess the protective effect of the agent. Numerous fatty deposits were observed in ethanol-induced fatty livers. These grew with the duration of cold storage. Hepatic transaminases of the effluents increased during cold preservation in the livers of alcohol-treated rats. Additionally, peroxidative lipids in the effluents increased during cold preservation in the livers of alcohol-treated rats, whereas they were undetectable in non-alcohol-treated rat livers. The sinusoidal endothelium had severely deteriorated in the livers of alcohol-treated rats. Further, the HUR decreased with ethanol treatment and/or cold preservation. The addition of hrHGF suppressed the increase of hepatic transaminase in the effluent of cold-preserved alcohol-treated livers. Peroxidative lipids in the same effluents were undetectable. In fatty livers, both hepatocytes and SECs received severe damage during cold preservation. Furthermore, we demonstrated that hepatocellular injury was significantly inhibited by hrHGF.
酒精摄入所致的脂肪肝通常不适合用于移植。在本研究中，我们调查了酒精性脂肪肝冷保存期间肝细胞和肝窦内皮细胞（SECs）的损伤情况，并检测了重组人肝细胞生长因子（hrHGF）的疗效。给大鼠喂食酒精饲料。我们对肝细胞进行了组织学检查，并观察了SECs的超微结构改变。此外，我们测量了肝转氨酶和过氧化脂质以评估肝细胞损伤情况，并测定了透明质酸摄取率（HUR）以确定SECs损伤情况。我们将hrHGF添加到威斯康星大学（UW）溶液中以评估该药物的保护作用。在乙醇诱导的脂肪肝中观察到大量脂肪沉积。这些脂肪沉积随着冷藏时间的延长而增加。在酒精处理大鼠肝脏的冷保存过程中，流出液中的肝转氨酶升高。此外，在酒精处理大鼠肝脏的冷保存过程中，流出液中的过氧化脂质增加，而在未用酒精处理的大鼠肝脏中未检测到。在酒精处理大鼠的肝脏中，肝窦内皮严重受损。此外，乙醇处理和/或冷保存会使HUR降低。添加hrHGF可抑制冷保存的酒精处理肝脏流出液中肝转氨酶的升高。相同流出液中的过氧化脂质未被检测到。在脂肪肝中，肝细胞和SECs在冷保存期间均受到严重损伤。此外，我们证明hrHGF可显著抑制肝细胞损伤。
