Liu Xu-hua, Chen Yu, Wang Tai-ling, Lu Jun, Zhang Li-jie, Song Chen-zhao, Zhang Jing, Duan Zhong-ping
Artificial Liver Treatment and Training Center, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
Zhonghua Gan Zang Bing Za Zhi. 2007 Oct;15(10):771-5.
To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment.
Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.
Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure.
We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.
建立一种实用且可重复的人类慢加急性肝衰竭动物模型，用于进一步研究慢加急性肝衰竭的病理生理机制以及其治疗中的药物筛选和评价。
用人类血清白蛋白诱导Wistar大鼠发生免疫性肝纤维化。在早期肝硬化（纤维化IV期）大鼠中，给予D-半乳糖胺和脂多糖。记录20只大鼠的死亡率和生存时间。在4、8和12小时处死10只大鼠。给予D-半乳糖胺/脂多糖后检测肝功能和血浆细胞因子水平，并研究肝脏病理学。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测细胞凋亡。
大多数用人白蛋白处理的大鼠发生了肝硬化和纤维化，其中90%在给予D-半乳糖胺/脂多糖后死于急性肝衰竭，平均生存时间为（16.1±3.7）小时。肝脏组织病理学显示再生结节有大片或亚大片坏死，而纤维间隔完整。肝功能检测结果与肝细胞大片坏死相符。血浆TNFα水平显著升高，与肝细胞凋亡程度平行。血浆IL-10水平的升高与慢加急性肝衰竭患者相似。
我们通过用人血清白蛋白处理大鼠，随后给予D-半乳糖胺和脂多糖，建立了慢加急性肝衰竭动物模型。TNFα介导的肝细胞凋亡在急性肝衰竭发病机制中起非常重要的作用。
