FR167653在犬全肝血管阻断模型中的作用。

The effect of FR167653 in a canine total hepatic vascular exclusion model.

作者信息

Sunose Yutaka, Takeyoshi Izumi, Tsutsumi Hirofumi, Kawata Kiyoshi, Iwazaki Shigeru, Matsumoto Koshi, Ohwada Susumu, Morishita Yasuo

机构信息

Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.

出版信息

Hepatogastroenterology. 2003 Jan-Feb;50(49):161-4.

PMID:12630014

Abstract

BACKGROUND/AIMS: Though liver grafts from non-heart-beating donors are now attracting much attention, these grafts inevitably suffer from severe warm ischemia. The aim of this study was to evaluate the effect of TNF-alpha and IL-1 suppression on warm ischemia-reperfusion injury in a canine total hepatic vascular exclusion model.

METHODOLOGY

Warm ischemia was induced by 1-h total hepatic vascular exclusion with active splenofemuro-juglar bypass. Animals were divided into two groups. FR167653 (1 mg/kg/hr) was administered via the portal vein from 30 min prior to ischemia until 2 h after reperfusion to the FR group (n = 7), and a vehicle was administered to the control group (n = 7). The serum alanine aminotransferase, aspartate amino-transferase, lactate dehydrogenase, and hyaluronic acid levels were measured. Hepatic tissue blood flow was also measured. Liver specimens were harvested for histological study, and polymorphonuclear neutrophils were counted.

RESULTS

Serum liver enzymes were significantly (p < 0.05) lower, and hepatic tissue blood flow was kept significantly (p < 0.05) better in the FR group than in the control. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p < 0.05) lower in the FR group than in the control group.

CONCLUSIONS

FR167653 provides protective effects on hepatic warm ischemic injury in a canine total hepatic vascular exclusion model.

摘要

背景/目的：尽管来自非心跳供体的肝移植目前备受关注，但这些移植物不可避免地会遭受严重的热缺血。本研究的目的是评估在犬全肝血管阻断模型中，肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）抑制对热缺血再灌注损伤的影响。

方法

通过1小时的全肝血管阻断并进行主动脾-股静脉-颈静脉旁路来诱导热缺血。将动物分为两组。在缺血前30分钟至再灌注后2小时，通过门静脉向FR组（n = 7）给予FR167653（1毫克/千克/小时），向对照组（n = 7）给予赋形剂。测量血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、乳酸脱氢酶和透明质酸水平。还测量肝组织血流量。采集肝脏标本进行组织学研究，并对多形核中性粒细胞进行计数。