STUDIES ON HOST FACTORS RELATED TO FULMINANT HEPATITIS

暴发性肝炎是一种预后不良的肝病，其特征是肝细胞大量死亡和肝再生不良，然而，与暴发性肝炎相关的宿主因素尚不清楚。首先，我们使用内部微阵列全面分析了小鼠肝再生过程中基因表达的变化。参与蛋白质合成和翻译后加工的基因在以快速基因激活为特征的簇中富集。血浆，蛋白质分泌和中间代谢的基因丰富的集群表现出逐渐的基因激活的功能。因此，聚类分析功能分类基因的表达模式，深入了解肝再生的机制和病理生理。然后，在卵圆细胞诱导模型，模拟暴发性肝炎，基因表达谱也进行了检查。包括骨桥蛋白在内的4个基因在这些模型中表达上调，提示这些基因可能与重型肝炎的发生有关。重型肝炎患者血清骨桥蛋白水平明显高于急性自限性肝炎患者。进一步的研究是揭示骨桥蛋白在暴发性肝炎发展过程中的作用的唯一途径。

Fulminant hepatitis is a poor prognostic liver disease characterized with massive death of hepatocytes and poor liver regeneration, however, host factors related to the fulminant hepatitis is not well known. First, we comprehensively analyzed the changes in gene expression during mouse liver regeneration using an in-house microarray. Genes involved in protein synthesis and posttranslational processing were enriched in the cluster characterized by rapid gene activation. Genes for plasma, protein secretion and intermediate metabolism were enriched in clusters exhibiting the features of gradual gene activation. Thus, clustering analysis of expression patterns of functionally classified genes gave insights into mechanism and pathophysiology of liver regeneration. Then, the gene expression profiles in oval cell induction models, mimicking fulminant hepatitis, were also examined with DNA microarray. Four genes including osteopontin were up-regulated in these models suggesting that these genes might be related to the development of fulminant hepatitis. The serum osteopontin level was revealed to be significantly higher in patients with fulminant hepatitis compared to those with acute self limited hepatitis. Further studies is uncle way to reveal the role of osteopontine during the development of fulmimant hepatitis.