Shimizu H, Miyazaki M, Ito H, Nakagawa K, Ambiru S, Kato A, Nukui Y, Nozawa S, Nakajima N
First Department of Surgery, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan.
Hepatogastroenterology. 2001 Jan-Feb;48(37):216-9.
BACKGROUND/AIMS: The purpose of this study was to clarify the mechanism of cold ischemia-reperfusion-induced graft injury after liver transplantation, especially with regard to the relationship between hepatocyte, sinusoidal endothelial cell injury, and hepatic hemodynamic alteration.
We evaluated changes in hepatocyte and sinusoidal endothelial cell function, and hepatic hemodynamics after reperfusion in an isogeneic rat liver-transplantation model. The livers of male LEW rats were stored in 4 degrees C lactated Ringer's solution for 1 hr, 3 hr (viable graft), and 6 hr (nonviable graft) before implantation. After reperfusion, hepatocyte function was assessed by serum alanine aminotransferase level and bile output; sinusoidal endothelial cell function was evaluated by serum hyaluronic acid level. Furthermore, we measured hepatic venous oxygen saturation, and portal venous blood flow using a transit time blood flow meter.
At 2 hr after reperfusion, the hepatocyte function was similar in all groups. However, the sinusoidal endothelial cell function deteriorated severely in the nonviable graft group, and significantly decreased hepatic venous oxygen saturation levels were observed, suggesting poor hepatic circulation. At 4 hr after reperfusion, the hepatocyte injury was markedly increased in the nonviable graft group. Although systemic blood pressure remained stable, significantly decreased portal venous blood flow in the nonviable graft group was found compared with the viable graft groups. Histopathological studies showed that massive ischemic necrosis was seen in zone III (central) of hepatic lobule 8 hr after reperfusion in the nonviable graft group.
These data suggest that the sinusoidal endothelial cell injury was predominant in the early phase of reperfusion, and might cause microcirculatory disturbances, resulting in decreased portal venous blood flow. This phenomenon may subsequently cause ischemic damage to the hepatocyte, with eventual graft failure.
背景/目的：本研究旨在阐明肝移植后冷缺血-再灌注诱导移植物损伤的机制，尤其是肝细胞、肝血窦内皮细胞损伤与肝脏血流动力学改变之间的关系。
我们在同基因大鼠肝移植模型中评估了再灌注后肝细胞和肝血窦内皮细胞功能以及肝脏血流动力学的变化。雄性LEW大鼠的肝脏在植入前于4℃乳酸林格液中保存1小时、3小时（存活移植物）和6小时（非存活移植物）。再灌注后，通过血清丙氨酸氨基转移酶水平和胆汁分泌量评估肝细胞功能；通过血清透明质酸水平评估肝血窦内皮细胞功能。此外，我们使用渡越时间血流仪测量肝静脉血氧饱和度和门静脉血流量。
再灌注后2小时，所有组的肝细胞功能相似。然而，非存活移植物组的肝血窦内皮细胞功能严重恶化，观察到肝静脉血氧饱和度水平显著降低，提示肝脏循环不良。再灌注后4小时，非存活移植物组的肝细胞损伤明显增加。尽管全身血压保持稳定，但与存活移植物组相比，非存活移植物组的门静脉血流量显著降低。组织病理学研究显示，非存活移植物组再灌注8小时后肝小叶Ⅲ区（中央区）出现大量缺血坏死。
这些数据表明，肝血窦内皮细胞损伤在再灌注早期占主导地位，可能导致微循环障碍，从而使门静脉血流量减少。这种现象随后可能导致肝细胞缺血损伤，最终导致移植物功能衰竭。
