Mechanisns of Post-operatire Hepatic Failure after Extended Hepatectomy

扩大肝切除术后肝衰竭的机制

• 批准号: 07671363
• 负责人: MIYAZAKI Masaru
• 金额: $ 1.54万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671363/
• 关键词: Hepatic resection; Hepatic failure; Neutrophil; Inflammatory cytokine; Obstructive jaunfice; 活性化好中球

(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

(1)本研究旨在评估梗阻性黄疸(OJ)患者广泛肝切除术后肝功能衰竭可能是由中性粒细胞(PMN)介导的假说。在OJ组，大鼠在胆汁淤积2周后行78%的肝部分切除，随后胆道外引流5天。假手术对照组：假手术后第19天行大鼠部分肝切除。血清细胞因子诱导的中性粒细胞趋化因子(CINC)与人白介素8(IL-8)家族的生长相关癌基因(GRO)产物同源，是一种主要的中性粒细胞趋化因子，在大鼠胆汁淤积和随后的外引流过程中，随着PMN在肝窦内的积聚，CINC的浓度增加。然而，作为肝窦内皮细胞损伤标志物的血清嘌呤核苷磷酸化酶(PnP)/丙氨酸转氨酶(ALT)比值的变化没有显示出…的迹象两组间差异更显著。细胞间黏附分子-1(ICAM-1)的表达不受胆汁淤积和外引流的影响。肝部分切除后，OJ组较假手术对照组即刻血清CINC浓度升高更明显，血窦内PMN积聚更明显，持续时间更长。ICAM-1的表达在肝部分切除后24-48小时达到高峰。在这一高峰期，OJ组的PNP/ALT比值显著高于OJ组。提示胆汁淤积性广泛肝切除术后肝窦间隙中性粒细胞的积聚和SECs上ICAM-1的表达可能与SEC损伤的发生密切相关。(2)梗阻性黄疸患者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发生机制。然而，将中性粒细胞与血管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来研究的报道很少。本研究旨在探讨中性粒细胞介导的内皮细胞损伤在梗阻性黄疸患者中的作用。将患者分为三组：肝脏正常组、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佛波醇醋酸酯后进行共培养。梗阻性黄疸缓解组乳酸脱氢酶和血栓调节蛋白的释放均显著高于肝功能正常组(P&lt；0.001)。梗阻性黄褐组与肝功能正常组比较差异无统计学意义。梗阻性黄疸缓解组中性粒细胞悬液中弹性蛋白酶活性明显高于肝功能正常组(P&lt；0.001)，提示梗阻性黄疸患者中性粒细胞在缓解期未被激活。梗阻性黄疸缓解后，中性粒细胞被强烈激活，有可能导致内皮细胞损伤。梗阻性黄疸患者中性粒细胞预充可能与术后并发症的频繁发生有关。

项目成果

Masaru Miyazaki: "Portal veiu reconstruction at the bepatic hilus using a left reual vein graft" Journal of the American college of Surgeons. 180. 497-498 (1995)

Masaru Miyazaki：“使用左真静脉移植物重建门静脉”美国外科医师学会杂志。

Kimura F.: "Reduced Hepatic Acute-Phase Reponse after Simultaneous Resection for Gastrointestinal Cancer with Synchronous Hepatic Metastases" Britisch Journal of Surgery. 83. 1002-1006 (1996)

Kimura F.：“伴有同步肝转移的胃肠癌同时切除后肝脏急性期反应减少”《英国外科杂志》。

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Kimura F.et al: "Reduced hepatic acute-phase response after simultaneous resection for gastrointestinal cancer with synchronous hepatic metastases." Br J Surg. 83. 6-1002 (1996)

Kimura F.等人：“同时切除胃肠癌伴同步肝转移后，肝脏急性期反应减少。”

Satoshi Ambiru: "Increased serum type TV collagw 7-S levels in patieuts with hepatic wetastasis" The American Journal of Gasfroeuterology. 90. 783-787 (1995)

Satoshi Ambiru：“肝湿瘀阻患者血清型 TV collagw 7-S 水平升高”《美国胃气学杂志》。