关键词: 急性肝损伤, 转录组, 高通量测序, 信号通路

Abstract: [Objective]To identify the key genes and signaling pathways associated with the occurrence and development of acetaminophen （APAP）-induced acute liver injury. [Method] An APAP-induced acute liver injury model was established in C57BL/6J mice. Two cDNA libraries from liver tissues of the healthy mice and the APAP-induced acute liver injury model mice on 2^nd day of modeling were constructed and used to perform RNA-seq, respectively. The obtained transcriptome sequencing data were de novo assembled and functionally annotated. DESeq R package （1.10.0） was used for identification of differentially expressed genes （DEGs）. KOBAS software was employed to conduct bioinformatics analysis on KEGG to determine the signaling pathways of DEGs enrichment associated with APAP-induced acute liver injury. [Result]Compared with the liver tissues of the healthy mice, a total of 7 270 DEGs were found in those of the modeling mice on 2^nd day of APAP-induced acute liver injury, of which 3 707 DEGs were significantly （P<0.05） up-regulated and 3 563 DEGs were significantly （P<0.05） down-regulated. Among the significantly up-regulated DEGs, Col1a1 was the most differentially expressed gene followed by Gsta1 and S100a6, and for the significantly down-regulated DEGs, the most differential expressions were observed in Slc1a2 followed by Glul and Acaa1b. Furthermore, a total of 2 515 DEGs were enriched in 316 different KEGG pathways. The significantly up-regulated DEGs were enriched in the signaling pathways of chemokine, B lymphocytes receptor, NOD-like receptor, ECM receptor interaction and some immune and inflammatory signaling pathways, while the significantly down-regulated DEGs were enriched in those of oxidative phosphorylation, fatty acids degradation and metabolism, carbon metabolism and some synthetic and metabolic signaling pathways. [Conclusion] Multiple signaling pathways are involved in the process of APAP-induced acute liver injury, among which chemokine signaling pathway and ECM receptor interaction signaling pathway may exert leading roles in acute injury phase.

Key words: acute liver injury, transcriptome, high-throughput sequencing, signaling pathway