FR167653·肝切除术·肝功能衰竭·肝硬化·大鼠

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

http://www.100md.com 《中国普通现代外科进展》 2006年第2期

FR167653·肝切除术·肝功能衰竭·肝硬化·大鼠,Wistar,,FR167653·肝切除术·肝功能衰竭·肝硬化·大鼠，Wistar,FR167653阻止肝硬化大鼠70%肝切除术后急性

     【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。

    【关键词】FR167653·肝切除术·肝功能衰竭·肝硬化·大鼠，Wistar

    FR167653 attenuates acute hepatic failure after partial hepatectomy in cirrhotic rats

    HOU Zhengsheng1,Kamohara Yukio2,Yanaga Katuhiko2

    1Department of hepaticobiliary Surgery,Peking University Shougang Hospital(Beijing 100041,China)

    2Department of Transplantation and Digestive Surgery,Graduate School of Biomedical Sciences,Nagasaki University(171 Sakamoto,8528501,Nagasaki Japan)

    【ABSTRACT】Objective:Proinflammatory cytokines such as tumor necrosis factorα(TNFα) and interleckin 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 FR167653(FR) attenuates an acute liver injury induced by the injection of Lipopolysaccharide (LPS) after partial hepatectomy in cirrhotic rats.Methods:Dimethylnitrosamineinduced cirrhotic rats received LPS 48h after 70% hepatectomy to prepare a lethal posthepatectomy acute liver failure model.FR was administered intravenously at 3mg/(kg·hour)for 150min,starting 30min before LPS challenge.Results:FR significantly improved the survival rate of rats at 48h after LPS challenge.Serum lev ......

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