大鼠慢加急性肝衰竭实验模型的建立及其病理机制初步研究  

Human Serum Albumin and A Rat's Model for D-Galactosamine/Lipopolysaccharide Induced Acute-on-Chronic Liver Failure

作　　者：刘旭华[1] 陈煜[1] 张晶[1] 丁美[1] 王泰龄[2] 段钟平[1] 

机构地区：[1]首都医科大学附属北京佑安医院人工肝中心,北京100069 [2]中日友好医院病理科,北京100029

出　　处：《科技导报》2007年第18期32-37,共6页Science & Technology Review

基　　金：科技部国家科技攻关引导项目(2003BA753C);首都医学发展科研基金重点项目(2003335)

摘　　要：慢加急性肝衰竭是我国最常见的肝衰竭类型,但目前国内外尚无此类肝衰竭动物模型的报道。本实验采用人血清白蛋白免疫诱导建立肝硬化大鼠模型,在此基础上予以D-氨基半乳糖/脂多糖联合急性攻击,90%大鼠死于肝衰竭,平均生存时间(16.1±3.7)h,动态观察转氨酶及胆红素变化符合肝细胞大片坏死时的功能改变,光镜下观察肝脏病理表现为肝硬化再生结节内发生大块或亚大块坏死,纤维间隔保留。血清TNF-!以给药后8h为最高,与TUNEL法检测原位细胞凋亡程度相一致。IL-10随给药时间延长而增高,与临床慢加急性肝衰竭患者变化相似。对人血清白蛋白免疫诱导型肝硬化大鼠给予D-氨基半乳糖/脂多糖联合急性攻击,可以建立慢加急性肝衰竭模型,本实验模拟了临床经常遇到的慢性肝病基础上发生急性肝衰竭的部分病理生理过程。TNF-!介导的肝细胞凋亡可能是该慢加急性肝衰竭的重要病理机制之一。There was no report on experimental model for acute-on-chronic liver failure, which is most commonly found in China. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats, then D-galactosamine/lipopolysaccharide was administered. 90% of rats died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with mean survival time of （16.1 ±3.7） hours. The kinetic changes of AST and TBil were compatible with massive necrosis of hepatocytes. Histopathological studies revealed massive or submassive necrosis in regenerative nodules, with fibrosis septa being kept intact. Plasma level of TNF-α was significantly increased 8 hours after administration of D-galactosamine /lipopolysaccharide, in association with apoptosis shown by TUNEL, while the profile of plasma IL-10 level was consistent with immunosuppression as seen in patients with acute-on-chronic liver failure. Animal model for acute-on-chronic liver failure can be established by treating human serum albumin-induced rat＇s cirrhosis with D-galactosamine/lipopolysaccharide. This model duplicated partly pathophysiological process as seen in acute liver failure developed on the chronic liver disease. TNF-α-mediated liver cell apoptosis plays a very important role in the pathogenesis.

关 键 词：慢加急性肝衰竭 动物模型 脂多糖 D-氨基半乳糖 

分 类 号：R-332[医药卫生] R575.3