生物信息学方法研究高脂饮食诱导肥胖对雄性SD大鼠的影响

摘要

目的 应用生物信息学方法探寻高脂饮食诱导性肥胖雄性SD大鼠生理代谢改变及对生育力的影响. 方法 利用NCBI中的GEO基因芯片公共数据库进行芯片数据搜索,最终选择芯片数据(GSE8700)作为分析对象,使用bioconductor包中R工具的函数及Limma程序包识别差异性表达基因,应用DAVID数据库对差异表达基因进行GO富集分析和KEGG通路分析,选用String在线数据库构建差异表达基因的PPI网络. 结果 通过对GSE8700进行分析,得到1 014个表达差异基因,其中上调基因544个,下调基因470个;上调差异基因GO条目全部富集于生物过程(BP),主要为氧化还原、轴突生成、对肽类激素反应、对糖皮质激素反应过程;下调差异基因GO富集于生物过程(BP),主要为女性怀孕、对类固醇激素的反应、甘油三酯代谢等过程;富集于细胞组成(CC),主要为细胞外间质,细胞质,血液微球等组成;富集于分子功能(MF),主要为丝氨酸肽链内切酶活性、脂肪酸结合、磷脂质结合等功能;上调差异基因并未富集到任何KEGG通路,而下调差异基因富集到3条通路,分别为PPAR信号通路(过氧化物酶体增殖物激活型受体)、脂肪的消化和吸收通路、胰腺分泌通路,其中重要的节点基因为热休克蛋白90AB1(Hsp90ab1)、细胞外钙敏感受体(Casr)及趋化因子9(Ccl9)等. 结论 高脂饮食诱导肥胖雄性SD大鼠脂质代谢发生了紊乱,大鼠生殖功能可能受到影响,类固醇激素、肽类激素代谢异常可能是其影响途径.%Objective: To investigate the effect of high-fat diet induced obesity on physiological metabolism and fertility in SD male rats.Methods: By using GEO gene chip common database in NCBI for chip data search,finally the chip data(GSE8700) was selected as the analysis object.The differentially expressed genes(DEGs) were identified by using R software in the bioconductor package and the Limma package.GO enrichment and KEGG pathway analysis were performed using DAVID online tool.Protein-protein interaction(PPI) network of the DEGs was constructed by String database.Results: A total of 1 014 genes were identified after analyzing GSE8700.Among them,544 genes were up-regulated and 470 genes were down-regulated.GO analysis results showed that up-regulated DEGs were significantly enriched in biological processes(BP),including oxidation-reduction process,axon formation and response to glucocorticoid.The down-regulated DEGs were significantly enriched in biological processes,including female pregnancy,response to steroid hormone and triglyceride metabolic process,etc.Go cell component(CC) analysis only displayed in down-regulated DEGs,including extracellular space,cytoplasm and blood microparticle.For molecular function(MF),the DEGs were enriched in serine-type endopeptidase activity,fatty acid binding and phospholipid binding;the up-regulated genes were not enriched in any KEGG pathway,and the down-regulated DEGs were enriched in PPAR signaling pathway,fat digestion and absorption,pancreatic secretion.The top 10 hub genes included heat shock protein 90 alpha family class B member 1(Hsp90ab1),calcium-sensing receptor(Casr),and chemokine(C-C motif) ligand 9(Ccl9),etc.Conclusions: High-fat diet induced obesity can lead to the lipid metabolism disorders in male rats.Obesity may affect the reproductive function of male rat.Its mechanism might be related to the metabolic abnormality of steroids hormone and peptide hormone.