Zheng Xiaoyang, Zhou Huaqiang, Qiu Zeting, Gao Shaowei, Wang Zhongxing, Xiao Liangcan
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Mol Med Rep. 2017 Sep;16(3):3299-3307. doi: 10.3892/mmr.2017.6966. Epub 2017 Jul 13.
Liver ischemia and reperfusion (I/R) injury is of primary concern in cases of liver disease worldwide and is associated with hemorrhagic shock, resection and transplantation. Numerous studies have previously been conducted to investigate the underlying mechanisms of liver I/R injury, however these have not yet been fully elucidated. To determine the difference between ischemia and reperfusion in signaling pathways and the relative pathological mechanisms, the present study downloaded microarray data GSE10657 from the Gene Expression Omnibus database. A total of two data groups from 1‑year‑old mice were selected for further analysis: i) A total of 90 min ischemia; ii) 90 min ischemia followed by 1 h of reperfusion, n=3 for each group. The Limma package was first used to identify the differentially expressed genes (DEGs). DEGs were subsequently uploaded to the Database for Annotation Visualization and Integrated Discovery online tool for Functional enrichment analysis. A protein‑protein interaction (PPI) network was then constructed via STRING version 10.0 and analyzed using Cytoscape software. A total of 114 DEGs were identified, including 21 down and 93 upregulated genes. These DEGs were primarily enriched in malaria and influenza A, in addition to the tumor necrosis factor and mitogen activated protein kinase signaling pathways. Hub genes identified in the PPI network were C‑X‑C motif chemokine ligand (CXCL) 1, C‑C motif chemokine ligand (CCL) 2, interleukin 6, Jun proto‑oncogene, activator protein (AP)‑1 transcription factor subunit, FOS proto‑oncogene, AP‑1 transcription factor subunit and dual specificity phosphatase 1. CXCL1 and CCL2 may exhibit important roles in liver I/R injury, with involvement in the immune and inflammatory responses and the chemokine‑mediated signaling pathway, particularly at the reperfusion stage. However, further experiments to elucidate the specific roles of these mediators are required in the future.
肝缺血再灌注（I/R）损伤是全球肝病病例中的主要关注点，与失血性休克、肝切除和肝移植相关。此前已经进行了大量研究来探究肝I/R损伤的潜在机制，然而这些机制尚未完全阐明。为了确定信号通路中缺血和再灌注之间的差异以及相关的病理机制，本研究从基因表达综合数据库下载了微阵列数据GSE10657。总共选择了来自1岁小鼠的两个数据组进行进一步分析：i）总共90分钟缺血；ii）90分钟缺血后再灌注1小时，每组n = 3。首先使用Limma软件包来识别差异表达基因（DEG）。随后将DEG上传到在线工具数据库进行注释、可视化和综合发现以进行功能富集分析。然后通过STRING 10.0构建蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape软件进行分析。总共鉴定出114个DEG，包括21个下调基因和93个上调基因。这些DEG主要富集于疟疾和甲型流感，此外还涉及肿瘤坏死因子和丝裂原活化蛋白激酶信号通路。在PPI网络中鉴定出的枢纽基因有C-X-C基序趋化因子配体（CXCL）1、C-C基序趋化因子配体（CCL）2、白细胞介素6、原癌基因Jun、激活蛋白（AP）-1转录因子亚基、原癌基因FOS、AP-1转录因子亚基和双特异性磷酸酶1。CXCL1和CCL2可能在肝I/R损伤中发挥重要作用，参与免疫和炎症反应以及趋化因子介导的信号通路，特别是在再灌注阶段。然而，未来还需要进一步的实验来阐明这些介质的具体作用。
