Mechanisns of Post-operatire Hepatic Failure after Extended Hepatectomy

(1)本研究的目的是评估梗阻性黄疸（OJ）患者广泛肝切除术后肝功能衰竭可能由多形核中性粒细胞（PMN）介导的假设。在OJ组，经过2周的胆汁淤积和5天的外胆道引流后，大鼠接受了78%的部分肝切除术。假手术对照组在假手术后19天切除部分肝。血清细胞因子诱导的中性粒细胞趋化剂（CINC）与生长相关癌基因（gro）产物同源，是人白细胞介素(IL) -8家族的一员，是大鼠中一种主要的中性粒细胞趋化因子，在胆汁淤积和随后的体外引流期间，随着pmn在肝窦的积累，CINC的浓度随之增加。而血清嘌呤核苷磷酸化酶(PNP) /丙氨酸转氨酶（ALT）比值作为窦状内皮细胞（SEC）损伤的标志物，在两组间无明显差异。细胞间粘附分子-1 （ICAM-1）在SECs上的表达不受胆汁淤积和体外引流的影响。肝部分切除术后，OJ组的血清CINC浓度比假手术对照组立即升高更为显著，且假手术对照组pmn在窦内的积聚更为明显且持续时间更长。ICAM-1表达在两组均有增强，在肝部分切除后24 - 48小时达到峰值。在这个高峰期，OJ组的PNP/ALT比值显著升高。上述结果提示，肝窦间隙中pmn的积累和肝窦内壁上ICAM-1的表达可能与肝窦内壁大范围切除后胆汁淤积患者肝窦内壁损伤的发生密切相关。(2)梗阻性黄疸术后并发症发生率高。最近的报道显示，中性粒细胞参与了术后并发症的机制。然而，关于中性粒细胞和内皮细胞之间的相互作用作为阻塞性黄疸炎症反应的初始事件的研究报道很少。本研究的目的是评估中性粒细胞介导的内皮细胞损伤在梗阻性黄疸患者。将患者分为肝功能正常组、梗阻性黄疸组、梗阻性黄疸缓解组。分别从患者外周血中分离中性粒细胞。人脐静脉内皮细胞与中性粒细胞在加入肉豆蔻酸佛波酯后共培养。测定培养液中LDH和血栓调节素的释放。梗阻性黄疸缓解组LDH和血栓调节素的释放量显著高于肝正常组（p<0.001）。梗阻性黄疸组与肝正常组比较无显著性差异。梗阻性黄疸缓解组中性粒细胞悬液弹性酶活性同样高于肝脏正常组（p<0.001）。本研究提示梗阻性黄疸患者中性粒细胞在缓解前未被激活。梗阻性黄疸缓解后，中性粒细胞被强烈激活，有可能引起内皮细胞损伤。中性粒细胞“启动”可能与阻塞性黄疸患者术后并发症的频繁发生有关。少

(1) The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in Patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL) -8 family, and a major neutrophil chemtactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP) / alanine transaminase (ALT) ratio as a maker of sinusoidal endothelial cell (SEC) injury showed no sign … More ificant differences between the two groups. Intercellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both froups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.(2) A high incidence of complications has been documented in patients with obstructive jaundice after surgical operations. Recent reports have revealed that neutrophils are involved in the mechanism of postoperative complications. However, there are few reports investigating the interaction between neutrophils and endothelial cells as an initial event in inflammatory response in obstructive jaundice. The aim of this study was to evaluate neutrophil-mediated-endothelial cell injury in patients with obstructive jaundice.Patients were divided into three froups : those with normal liver, obstructive jaundice, relief of obstructive jaundice. Neutrophils were isolated from peripheral blood of patients individually. Human umbilical vein endothelial cells and neutrophils were co-cultured after addition of phorbol myristate acetate. The release of LDH and thrombomodulin was measured in the medium.The release of both LDH and thrombomodulin in the group with relief of obstructive jaundice was significantly higher than in the group with normal liver (p<0.001). There was no significant difference between the group with obstructive jaundice and the group with normal liver. The elastase activity in neutrophils suspension was similarly higher in the group with relief of obstructive jaundice than in the group with normal liver (p<0.001).This study suggests that neutrophils in patients with obstructive jaundice are not be activate before its relief. After relief of obstructive jaundice, neutrophils are strongly primed and have a potential to cause endothelial cell injury. The neutrophil "priming patients with obstructive jaundice might be associated with the frequent occurrence of postoperative complications. Less