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FR-167653阻止肝硬化大鼠70%肝切除术后急性肝功能衰竭的实验研究

FR-167653 attenuates acute hepatic failure after partial hepatectomy in cirrhotic rats
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摘要 目的探索肿瘤坏死因子-α及白介素-1β双重合成阻断剂-FR-167653在阻止内毒素诱发的肝硬化大鼠70%肝切除术后急性肝功能衰竭中的作用。方法切除二甲基亚硝胺诱导的肝硬化大鼠70%肝脏,48h后静脉注射脂多糖(LPS)诱发急性肝功能衰竭,FR-167653自LPS静脉注射前30min开始静脉给药150min,并设对照组,比较两组存活率、ALT、AST、TNF-α、IL-1β水平及病理改变。结果LPS注药后48h,实验组的生存率明显高于非给药对照组。6hTNF-α及IL-1β血清浓度,6,12hALT和AST血清浓度,两组差异有统计学意义。FR-167653给药减轻了LPS诱发的肝细胞坏死,及肝窦内炎细胞浸润。结论FR-167653能有效阻止内毒素诱发的肝硬化大鼠70%肝切除术后急性肝功能衰竭。 Objective： Proinflammatory cytokines such as tumor necrosis factor-α（TNF-α） and interleckln 1-β（IL-1β）play an important role in the development of hepatic failure after extensive liver resection. FR167653 has been characterized as a potent suppressant of TNF-α and IL-1β. In the present study,we explored the possibility that FR161653（FR） attenuates an acute Ilver InJury Induced by the injection of Lipopolysaccharide （LPS） after partial hepatectomy In clrrhotlc rats. Methods： Dimethylnltrosamine-lnduoed olrrlqotic rats received LPS 48h after 1096 hepatectomy to prepare a lethal posthepatectomy acute liver failure model. FR was adminlstered intravenously at 3mg/（kg·hour）for 150min, starting 30min before LPS challenge, Rsuits ：FR slgnlflcantly Improved the survival rate of rats at 48h after LPS challenge. Serum levels of alanine ：cransaminase （ ALT ）, asPartate transamlnase （ AST ）, TNF - α and IL-1β were signficantly lower in the FR-treeted group than that in the control group.Histopethoiogically,liver tissue damege was milder in the FR-treated group than that in the control group.Conelusion：The results indicate that treatment with FR amelicrates an acute liver injury incuced by the injection of endotoxin after partial hepatectomy in cirrhotic rats.
作者 侯郑生 蒲原行雄 矢永胜彦
机构地区 北京大学首钢医院肝胆外科 日本长崎大学医学部附属医院移植消化外科
出处 《中国现代普通外科进展》 CAS 2006年第2期83-85,共3页 Chinese Journal of Current Advances in General Surgery
关键词 FR-167653 肝切除术 肝功能衰竭 肝硬化 大鼠 Wistar FR167653 Hepatectomy Liver fallure Liver cirrhosis Rats,Wistar
分类号 R657.31 [医药卫生—外科学]
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参考文献17

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中国现代普通外科进展
2006年 第2期

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