暴发性肝炎是一种严重的肝脏疾病，表现出大量肝细胞坏死，伴随着肝功能衰竭的临床症状。无论是病毒性和自身免疫性肝炎，巨噬细胞和T细胞的活化是肝损伤和暴发性肝脏疾病的发病过程中关键的初始步骤，然而其内在的分子机制尚不明确。越来越多的研究表明，micrornA(miRNA)在人类疾病发生发展中发挥重要的调控作用。

浙江大学朱海红副研究员领衔的团队对刀豆蛋白A(Con A)诱发肝炎的早期阶段中的miRNA表达谱进行了深入分析，研究成果发表在7月刊的Cellular Physiology and Biochemisrty上。

研究人员分Balb/c小鼠注射刀豆注射剂，诱发暴发性肝炎，然后利用微阵列芯片对其肝组织中的miRNA表达谱进行分析(miRNA芯片项目由联川生物承担完成)。研究发现11种miRNAs在暴发性肝炎的早期肝组织与正常对照组肝组织之间存在显著差异表达。其中，Mmu-miR-133a的差异表达最明显，且具有最强的调控能力，可以调节47个mRNAs。Mmu-miR-10a在miRNA-GO-网络中表达水平最高，同样具有很强的调控能力。miR-133a和miR-10a的表达谱可被RT-PCR所验证。

此研究结果表明，在早期阶段，ConA诱发的暴发性肝炎诱导明显差异的miRNA表达谱。该差异的miRNA表达谱可以在急性和严重的肝脏疾病中提供致病线索，潜在诊断和预后的标志物。

原文摘要：

MicroRNA Expression Profiles Related to Early Stage Murine Concanavalin A-Induced Hepatitis

Jia H.-Y· Chen F · Chen J.-Z. Wu S.-S. Wang J. Cao Q.-Y.Chen Z.Zhu H.-H

Background: Fulminant hepatitis is a severe liver disease characterized by massive hepatocyte necrosis and clinical signs of liver failure. This study explores the expression profile of microRNAs, which are regulators of a number of pathophysiological processes, during the early stage of concanavalin A (Con A)-induced hepatitis.

Methods: Balb/c mice were given ConA injections to induce fulminant hepatitis. miRNA expression profiling in liver tissues was carried out by microarray analysis. The differentially expressed miRNAs were subjected to time sequence profile analysis, gene-miRNA regulatory network analysis, and gene ontology-miRNA regulatory network analysis.

Results:Eleven miRNAs among multiClass were found to be significantly differentially expressed between liver tissue in early stage fulminant hepatitis and normal control liver tissue. Mmu-miR-133a was the most differentially expressed with the strongest regulatory ability, regulating 47 mRNAs. Mmu-miR-10a was the most highly expressed in the microRNA-GO-Network and also exerted a strong regulatory ability. The expression profiles of miR-133a and miR-10a were verified by RT-PCR.

Conclusions: These results show that, in the early stage, ConA-induced fulminant hepatitis induces a distinct miRNA expression profile. This differential miRNA expression profile may provide pathogenic clues and potential diagnostic and prognostic markers in acute and severe liver disease.

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