Arii S, Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
J Gastroenterol Hepatol. 1995;10 Suppl 1:S92-6. doi: 10.1111/j.1440-1746.1995.tb01810.x.
Primary graft non-function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non-function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)alpha, and then increased ICAM-1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti-TNF alpha antibody and anti-ICAM-1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2-thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM-1, cytokines and prostanoids.
肝原发性移植肝无功能是再次移植的常见原因之一。虽然原发性移植肝无功能的机制尚未完全明了，但一个有力的解释性发病机制是冷保存和再灌注期间由于肝血窦损伤导致的微循环障碍。在本文中，我们讨论了肝血窦内皮细胞和库普弗细胞（KC）在冷保存/再灌注损伤中可能发挥的作用。在冷保存及随后的再灌注过程中，库普弗细胞被激活，内皮细胞受损。激活的KC产生大量肿瘤坏死因子（TNF）α，进而增加肝血窦内皮细胞中细胞间黏附分子-1（ICAM-1）的表达。再灌注实验表明，肝脏中的高凝状态和白细胞黏附与再灌注损伤密切相关，而阻断KC以及使用抗TNFα抗体和抗ICAM-1抗体可减轻损伤，同时伴有纤维蛋白沉积和白细胞聚集的减少。超微结构观察也显示阻断KC对维持肝血窦内皮细胞有有益作用。此外，还发现肝血窦中的血栓素A2-血栓素A2受体系统也参与了这一发病机制。因此，这些结果提示冷保存/再灌注损伤是由于肝血窦微循环障碍所致，这至少部分是由激活的KC与肝血窦内皮细胞之间通过ICAM-1、细胞因子和前列腺素等进行的相互作用所诱导的。
