Caraceni Paolo, Domenicali Marco, Maria Pertosa Anna, Maiolini Elisabetta, Grattagliano Ignazio, Principe Alessandro, Palasciano Giuseppe, Trevisani Franco, Bernardi Mauro
Department of Internal Medicine, Cardioangiology, and Hepatology, University of Bologna, Bologna, Italy.
J Surg Res. 2005 Aug;127(2):190-6. doi: 10.1016/j.jss.2005.02.018. Epub 2005 Apr 14.
Microcirculation disturbances are essential factors of preservation injury in fatty liver. However, hepatocyte injury is also markedly excessive in fatty liver resulting, at least in part, from energy metabolism impairment and oxidative stress. Thus, this study aimed to determine whether nutritional status influences preservation injury in fatty liver and whether energetic substrate supplementation, alone or with a vasodilator, is protective.
Normal or fatty livers induced by a choline-deficient diet were isolated from fed and fasted rats, preserved in University of Wisconsin solution at 4 degrees C for 18 h, and then reperfused with Krebs-Henseleit solution at 37 degrees C for 120 min. Fasted rats with fatty liver were also treated as follows: (1) Glucose supplementation: rats had access to a glucose solution for 18 h prior procurement; (2) Prostaglandin (PG): alprostadil was continuously infused during reperfusion; (3) Combined treatment: Glucose supplementation + PG.
Fasting-induced liver injury was significantly greater in fatty than normal liver. In fatty livers from fasted rats, all treatments reduced the alanine aminotransaminase release. Hepatic oxygen consumption improved in the glucose and glucose + PG groups, while PG infusion had no effect. Glucose supplementation did not affect portal pressure, which, in contrast, was reduced in livers receiving PG. Finally, all treatments lowered oxidative injury.
Preservation injury in fatty liver is greatly related to nutritional status. Energetic substrate supplementation may represent a clinically feasible protective strategy and a multistep approach adding vasodilators could offer further benefit by acting on different pathogenetic mechanisms.
微循环障碍是脂肪肝保存损伤的重要因素。然而，脂肪肝中的肝细胞损伤也明显过度，至少部分是由能量代谢受损和氧化应激导致的。因此，本研究旨在确定营养状况是否影响脂肪肝的保存损伤，以及单独或与血管扩张剂联合补充能量底物是否具有保护作用。
从喂食和禁食的大鼠中分离出由胆碱缺乏饮食诱导的正常或脂肪肝，在4℃下于威斯康星大学溶液中保存18小时，然后在37℃下用克雷布斯 - 亨泽莱特溶液再灌注120分钟。患有脂肪肝的禁食大鼠也按以下方式处理：（1）补充葡萄糖：大鼠在取材前18小时可饮用葡萄糖溶液；（2）前列腺素（PG）：在再灌注期间持续输注前列地尔；（3）联合治疗：补充葡萄糖+PG。
禁食诱导的肝损伤在脂肪肝中比正常肝脏明显更严重。在禁食大鼠的脂肪肝中，所有治疗均降低了丙氨酸转氨酶的释放。葡萄糖组和葡萄糖+PG组的肝脏氧消耗有所改善，而输注PG则没有效果。补充葡萄糖不影响门静脉压力，相反，接受PG的肝脏门静脉压力降低。最后，所有治疗均降低了氧化损伤。
脂肪肝的保存损伤与营养状况密切相关。补充能量底物可能是一种临床上可行的保护策略，通过作用于不同的发病机制，添加血管扩张剂的多步骤方法可能会带来进一步的益处。
