中国实验动物学报2025，Vol.33Issue(2)：204-215,12.DOI:10.3969/j.issn.1005-4847.2025.02.005
Lieber-DeCarli酒精性肝损伤小鼠模型的转录组学分析
Transcriptomics of the Lieber-DeCarli mouse model of alcoholic liver injury
摘要
Abstract
Objective To investigate the characteristics of liver injury in the Lieber-DeCarli alcoholic liver disease(ALD)mouse model and to analyze its transcriptomic profile.Methods Eighteen male C57BL/6J mice were randomly divided into an alcohol-fed group(n = 10)and a control group(n = 8).The alcohol-fed group received a Lieber-DeCarli ethanol diet,starting with an adaptive one-week phase using incremental concentrations of ethanol(10～57.3 mL/L),followed by 2 weeks of a 57.3 mL/L concentration of 95％ethanol,for a total of 3 weeks.The control group was provided with an isocaloric control diet for 3 weeks.At the end of the study,mice were sacrificed,and serum and liver tissue samples were collected.Serum liver function markers(ALT,AST),hepatic lipids(TC,TG),reduced glutathione(GSH),total superoxide dismutase(T-SOD),and malondialdehyde(MDA)were measured using biochemical assays.The levels of inflammatory cytokines(IL-6,IL-10,TNF-α,TGF-β1)in liver tissue were assessed by ELISA.Histopathological changes in liver tissue were examined using hematoxylin-eosin(HE)and Oil Red O staining.Immunohistochemical staining using the F4/80 antibody was employed to assess changes in macrophage expression.RNA-seq analysis was conducted to identify differentially expressed genes between the two groups of liver tissues,followed by GO and KEGG pathway enrichment analysis.qRT-PCR was used to validate the expression of these differentially expressed genes.Results Compared with the control group,the alcohol-fed mice exhibited a significant decrease in body weight(P<0.01).Serum ALT and AST levels were significantly elevated(P<0.01),while liver tissue levels of TC,TG,and MDA were significantly increased(P<0.05).Conversely,GSH and T-SOD levels were significantly reduced(P<0.05).The levels of inflammatory factors IL-6,TNF-α,and TGF-β1 were increased,which was consistent with the qRT-PCR validation results(P<0.05).Histological examination revealed disrupted hepatic lobular structure,with macrovesicular steatosis,microvesicular steatosis,and ballooning degeneration.Additionally,fat droplets in liver tissue were significantly increased,and macrophage expression was upregulated.Differential gene expression analysis,using a threshold of|log2 FC|>1 and q<0.05,identified 2063 differentially expressed genes,of which 1236 were upregulated and 827 downregulated.Enriched pathways included xenobiotic metabolism via cytochrome P450,cytokine-cytokine receptor interaction,chemokine signaling,steroid hormone biosynthesis,glutathione metabolism,and retinol metabolism.(P<0.05).qRT-PCR validation confirmed the significant upregulation(e.g.,Mmp12,Gstm3,Cyp2a22)and downregulation(e.g.,Serpina1e,Acmsd,Mup3d)of 10 genes from each category,consistent with the transcriptome sequencing results.Conclusions The primary pathological mechanisms underlying alcoholic liver injury involve pathways related to xenobiotic metabolism and act via cytochrome P450,cytokine-cytokine receptor interaction,chemokine signaling,glutathione metabolism,and retinol metabolism.关键词
酒精性肝损伤/Lieber-DeCarli模型/基因表达/转录组学Key words
alcoholic liver injury/Lieber-DeCarli model/gene expression/transcriptomics分类
生物学引用本文复制引用
阮天音,王四园,李旭涛,张昊,彭渊,刘成海,陶艳艳..Lieber-DeCarli酒精性肝损伤小鼠模型的转录组学分析[J].中国实验动物学报,2025,33(2):204-215,12.基金项目
上海市科委创新项目(19401901500). Funded by Shanghai Science and Technology Commission Innovation Project(19401901500). （19401901500）
