miRNAs在大鼠酒精性肝损伤中的作用研究初探  

Role and mechanism of miRNAs in alcoholic liver injury in rats

作　　者：从美丽 刘涛[1] 费璇[2] 周蓓 孙建新[2] 赵效国[2] CONG Meili;LIU Tao;FEI Xuan;ZHOU Bei;SUN Jianxin;ZHAO Xiaoguo(School of Public Health,Xinjiang Medical University,Urumqi 830011;China.2.Animal Laboratory Center of Xinjiang Medical University,Urumqi 830011)

机构地区：[1]新疆医科大学公共卫生学院,乌鲁木齐830011 [2]新疆医科大学动物实验中心,乌鲁木齐830011

出　　处：《中国比较医学杂志》2023年第12期34-41,共8页Chinese Journal of Comparative Medicine

基　　金：新疆维吾尔自治区自然科学基金联合基金项目(2021D01C247)。

摘　　要：目的 探讨miRNAs在大鼠酒精性肝损伤病变过程中的作用及其机制。方法 将30只雄性SD大鼠随机分成模型组和对照组,模型组灌胃56%白酒,对照组灌胃蒸馏水,连续8周;解剖取肝组织,采用大鼠miRNA芯片对肝中miRNAs进行检测,对其表达量进行分析,对差异miRNA进行靶基因预测,并采用Gene Ontology(GO)和KEGG Pathway富集分析了解差异miRNA靶基因的功能,使用Cytoscape构建差异miRNA-mRNA-Pathway调控网络进一步筛选调控关键miRNA与关键通路,RT-qPCR对挑选的miRNA进行表达量验证分析。结果 通过比较分析模型组和对照组芯片数据,共筛选出差异表达miRNA 12个(P<0.05,Fold change≥2),其中上调2个,下调10个。差异miRNA靶基因GO分类注释显示,差异miRNA与信号转导、代谢过程、抗氧化活性、细胞杀伤、酶调控活性、生物调控等生物功能密切相关。差异miRNA靶基因KEGG Pathway通路分析显示,AMPK信号通路、PI3K-Akt信号通路、Hippo信号通路、Wnt信号通路、癌症、自噬、胰岛素抵抗、Ras等信号通路可能在酒精性肝损伤病变过程中发挥着重要的调控作用。通过构建差异miRNA-mRNA-Pathway调控网络筛选出的Hub miRNA和通路有miR-145-5p、miR-107-3p、miR-297、Hippo信号通路、癌症、PI3K-Akt信号通路、AMPK信号通路等。qRT-PCR结果显示挑选验证miRNA表达变化趋势和基因芯片结果一致。结论 本研究建立了大鼠酒精性肝损伤miRNA表达谱,提示miR-145-5p、miR-107-3p及miR-297可能在肝酒精性病变过程中起着重要的作用。Objective To investigate the role and mechanism of miRNAs in alcoholic liver injury in rats.Methods Thirty male SD rats were randomly divided into model and control groups.The model group was gavaged with 56%liquor and the control group was gavaged with distilled water for 8 weeks.Liver tissue was collected,miRNAs were analyzed,and target genes of differentially expressed miRNAs were predicted by a rat miRNA chip.Gene ontology(GO)and KEGG pathway enrichment analysis were used to understand the function of differentially expressed miRNA target genes.A differentially expressed miRNA-mRNA-pathway regulatory network was constructed using Cytoscape to further screen important regulatory miRNAs versus important pathways.RT-qPCR was performed for selected miRNAs to validate the expression analysis.Results Twelve differentially expressed miRNAs(P<0.05,Fold change≥2)were screened out,including two upregulated and 10 downregulated miRNAs by comparative analysis of microarray data between model and control groups.GO classification annotation of differential miRNA target genes showed close associations between differentially expressed miRNAs and biological functions such as signal transduction,metabolic processes,antioxidant activity,cell killing,enzyme regulatory activity and biological regulation.Differentially expressed miRNA target genes in KEGG pathway analysis revealed that the AMPK signaling pathway,PI3K-Akt signaling pathway,Hippo signaling pathway,Wnt signaling pathway,cancer,autophagy,insulin resistance,Ras signaling pathway,and other signaling pathways might play major regulatory roles in alcoholic liver injury lesions.Hub miRNAs and pathways screened by constructing the differentially expressed miRNA-mRNA-pathway regulatory network were miR-145-5p,miR-107-3p,miR-297,Hippo signaling pathway,cancer,PI3K-Akt signaling pathway,and AMPK signaling pathway.qRT-PCR validated the gene expression trends,and gene chip result were consistent.Conclusions We established an miRNA profile of alcoholic liver injury in rats,whic

关 键 词：酒精性肝损伤 MIRNA 靶基因 信号通路 

分 类 号：R-33[医药卫生]