中国血液净化

›› 2007, Vol. 6 ›› Issue (9): 496-499.

• 基础研究 • 上一篇    下一篇

慢加急性肝衰竭大鼠血清TNF-α、白介素-10及肝细胞凋亡的动态变化

张文中 刘旭华 赵 军 陈 煜 段钟平
  

  1. 100069 北京，首都医科大学附属北京佑安医院
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2007-09-12 发布日期:2007-09-12

  • Received:1900-01-01 Revised:1900-01-01 Online:2007-09-12 Published:2007-09-12

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摘要： 目的 建立大鼠慢加急性肝衰竭实验模型，观察其血清TNF-α、IL-10及肝细胞凋亡的动态变化。方法 首先用人血白蛋白建立大鼠肝硬化模型，至肝纤维化4级时予D-氨基半乳糖/脂多糖急性攻击，计算动物死亡率及生存时间，观察给药后4h、8h、12h肝功能、血清TNF-α、IL-10水平及病理变化，TUNEL法检测原位细胞凋亡，计算凋亡指数。 结果 D-氨基半乳糖/脂多糖攻击后90%大鼠死于急性肝衰竭，平均生存时间(16.1±3.7)h，转氨酶及胆红素的变化符合肝功能衰竭特点，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-α明显增高并与肝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。 结论 对人血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建立慢加急性肝衰竭模型。TNF-α介导的肝细胞凋亡可能是该慢加急性肝衰竭重要病理机制之一，提示早期给予人工肝及血液净化治疗清除炎性介质、阻断炎症反应可能对慢加急性肝衰竭起到一定防治作用。

关键词: 慢加急性肝衰竭, 动物模型, 脂多糖, D-氨基半乳糖, 肿瘤坏死因子-α

Abstract:

Objective To establish experimental model of acute on chronic liver failure in rats, describing the kinetic changes of serum TNF- ,IL-10 and hepatocytes apoptosis. Methods Immunological hepatic fibrosis was induced by human serum albumin injection in Wistar rats. In rats with fibrosis stage IV, D-galactosamine/lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours, respectively. Liver function parameters, serum TNF- ,IL-10 levels were measured after treatment with D-galactosamine/lipopolysaccharide, as well as liver pathology study. Cell apoptosis was detected by tunnel assay. Results 90% rats died from acute liver failure after administration of D-galactosamine /lipopolysaccharide, with mean survival time of (16.1 3.7) hours.Liver function tests were compatible with liver failure. Histopathology revealed massive or sunbmassive necrosis in regenerative nodules, while fibrosis septa were intact. Plasma level of TNF- significantly increased, in association with apoptosis, while profile of plasma IL-10 level was consistent with immunosuppression seen in patients with acute-on-chronic liver failure. Conclusion Experimental model of acute-on-chronic liver failure can be established successfully by administration of D-galactosamine/ lipopolysaccharide on the immunological-induced cirrhosis. TNF-mediated hepatocytes apoptosis may play very important role in the pathogenesis. This results indicated that early artificial liver or blood apheresis therapy which could remove inflammatory medium may be useful.

Key words: Animal model, Lipopolysaccharide, TNF-a

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