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暴發(fā)性肝炎是一種嚴(yán)重的肝臟疾病，表現(xiàn)出大量肝細(xì)胞壞死，伴隨著肝功能衰竭的臨床癥狀。無論是病毒性和自身免疫性肝炎，巨噬細(xì)胞和T細(xì)胞的活化是肝損傷和暴發(fā)性肝臟疾病的發(fā)病過程中關(guān)鍵的初始步驟，然而其內(nèi)在的分子機(jī)制尚不明確。越來越多的研究表明，micrornA(miRNA)在人類疾病發(fā)生發(fā)展中發(fā)揮重要的調(diào)控作用。

浙江大學(xué)朱海紅副研究員領(lǐng)銜的團(tuán)隊(duì)對(duì)刀豆蛋白A(Con A)誘發(fā)肝炎的早期階段中的miRNA表達(dá)譜進(jìn)行了深入分析，研究成果發(fā)表在7月刊的Cellular Physiology and Biochemisrty上。

研究人員分Balb/c小鼠注射刀豆注射劑，誘發(fā)暴發(fā)性肝炎，然后利用微陣列芯片對(duì)其肝組織中的miRNA表達(dá)譜進(jìn)行分析(miRNA芯片項(xiàng)目由聯(lián)川生物承擔(dān)完成)。研究發(fā)現(xiàn)11種miRNAs在暴發(fā)性肝炎的早期肝組織與正常對(duì)照組肝組織之間存在顯著差異表達(dá)。其中，Mmu-miR-133a的差異表達(dá)最明顯，且具有最強(qiáng)的調(diào)控能力，可以調(diào)節(jié)47個(gè)mRNAs。Mmu-miR-10a在miRNA-GO-網(wǎng)絡(luò)中表達(dá)水平最高，同樣具有很強(qiáng)的調(diào)控能力。miR-133a和miR-10a的表達(dá)譜可被RT-PCR所驗(yàn)證。

此研究結(jié)果表明，在早期階段，ConA誘發(fā)的暴發(fā)性肝炎誘導(dǎo)明顯差異的miRNA表達(dá)譜。該差異的miRNA表達(dá)譜可以在急性和嚴(yán)重的肝臟疾病中提供致病線索，潛在診斷和預(yù)后的標(biāo)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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