基于生物信息学筛选非酒精性脂肪性肝纤维化相关基因及潜在治疗药物  

Identification of non-alcoholic fatty liver fibrosis-related genes and potential therapeutic drugs based on bioinformatics

作　　者：杨婧[1] 赵耀伟 牛捷 王锐[1] YANG Jing;ZHAO Yao-wei;NIU Jie;WANG Rui(Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《药学学报》2021年第11期3091-3096,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81473359);黑龙江省自然科学基金面上资助项目(H201472);黑龙江省优秀青年人才项目(2020YQ05)。

摘　　要：利用生物信息技术检索非酒精性脂肪性肝纤维化基因芯片数据,筛选与非酒精性脂肪性肝纤维化相关差异表达基因及潜在治疗药物,为本病深入研究及治疗提供新思路。利用基因表达数据库(Gene Expression Omnibus,GEO)检索"非酒精性脂肪肝纤维化"词条,下载GSE109345芯片数据,利用BioJupie分析平台筛选对照组及纤维化模型组差异表达基因,对所获得差异基因进行GO功能分析、KEGG通路分析、蛋白互作网络分析并作可视化处理;最终通过Connectivity Map (CMap)数据平台,预测对非酒精性脂肪性肝纤维化具有潜在治疗效果的化合物。共筛选到109个差异表达基因,包括70个上调基因和39个下调基因;功能分析显示差异基因主要参与蛋白激酶B信号转导、胞外区功能、小分子结合等功能;通路分析显示差异基因参与视黄醇代谢通路、类固醇激素合成通路、花生四烯酸代谢通路;蛋白互作网络分析与非酒精性脂肪性肝纤维化相关的基因主要为金属蛋白酶组织抑制因子-1(metallopeptidase inhibitor 1, TIMP1)、CC趋化因子配体2 [chemokine (C-C motif) ligand 2, CCL2]、信号调节蛋白B1(recombinant signal regulatory protein beta 1, SIRPB1)、细胞色素P450 (cytochrome P450, CYP)等;CMap分析结果显示,吡格列酮、米多君和槟榔碱等化合物对非酒精性脂肪性肝纤维化具有潜在的治疗作用。通过筛选差异表达基因,明确在非酒精性脂肪性肝纤维化发展过程中相关基因及潜在治疗化合物,同时本研究为非酒精性脂肪性肝纤维化临床治疗和新药研发提供新思路和方案。To provide new ideas for further research and treatment of nonalcoholic fatty liver fibrosis, we used bioinformatics technology to search the gene microarray data related to this disease and identified differentially expressed genes and potential therapeutic drugs. Gene Expression Omnibus(GEO) was used to search the entry of "nonalcoholic fatty liver fibrosis";the GSE109345 microarray data was downloaded, the differentially expressed genes in the control group and the fibrosis model group were screened with the BioJupie analysis platform, and GO function, KEGG pathway, protein-protein interaction(PPI) network analysis and visualization were conducted for the differentially expressed genes. Finally, through the Connectivity Map(CMap) data platform, compounds with potential efficacy on nonalcoholic fatty liver fibrosis were predicted. A total of 109 differentially expressed genes were screened, including 70 up-regulated genes and 39 down-regulated genes. Functional analysis showed that differentially expressed genes were mainly involved in protein kinase B signal transduction, extracellular domain function, small molecule binding and other functions;pathway analysis showed that these genes participated in retinol metabolism, steroid hormone synthesis, and arachidonic acid metabolism;PPI network analysis showed that metallopeptidase inhibitor 1(TIMP1), chemokine(C-C motif) ligand 2(CCL2), recombinant signal regulatory protein beta 1(SIRPB1), and cytochrome P450(CYP) were the main genes related to nonalcoholic fatty liver fibrosis.CMap analysis showed that pioglitazone, midodrine, arecoline and other compounds had potential efficacy in nonalcoholic fatty liver fibrosis. Thus, by screening for differentially expressed genes, related genes and potential therapeutic compounds effective in the treatment of non-alcoholic fatty liver fibrosis can be identified, as well as new ideas and approaches for the clinical treatment of non-alcoholic fatty liver fibrosis.

关 键 词：非酒精性脂肪性肝纤维化 生物信息技术 差异表达基因 潜在药物 

分 类 号：R575[医药卫生—消化系统]