Ohtsuka M, Miyazaki M, Kondo Y, Nakajima N
First Department of Surgery, School of Medicine, Chiba University, Japan.
Hepatology. 1997 Mar;25(3):636-41. doi: 10.1002/hep.510250324.
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 chemotactic 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 marker of sinusoidal endothelial cell (SEC) injury showed no significant 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 groups 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.
梗阻性黄疸（OJ）患者广泛肝切除术后的肝衰竭可能由多形核中性粒细胞（PMN）介导。在OJ组中，大鼠在胆汁淤积2周后接受78%的部分肝切除术，随后进行5天的外引流胆汁。在假手术对照组中，大鼠在假手术后19天接受部分肝切除术。血清细胞因子诱导的中性粒细胞趋化因子（CINC）的浓度与生长相关癌基因（gro）产物同源，后者是人类白细胞介素（IL）-8家族的成员，也是大鼠主要的中性粒细胞趋化因子，在胆汁淤积和随后的外引流期间，其浓度随着PMN在肝血窦中的积聚而同步增加。然而，作为肝血窦内皮细胞（SEC）损伤标志物的血清嘌呤核苷磷酸化酶（PNP）/丙氨酸转氨酶（ALT）比值在两组之间没有显著差异。SEC上的细胞间黏附分子-1（ICAM-1）表达不受胆汁淤积和外引流的影响。部分肝切除术后，OJ组血清CINC浓度立即升高，比假手术对照组更显著，且前者肝血窦中PMN的积聚更明显且持续时间更长。两组中ICAM-1表达均增强，在部分肝切除术后24至48小时达到峰值。在此峰值期，OJ组观察到显著更高的PNP/ALT比值。这些结果表明，在胆汁淤积的情况下，广泛肝切除术后肝血窦空间中PMN的积聚和SEC上ICAM-1的表达可能与SEC损伤的发生密切相关。
