父代高血糖对子代肝脏脂质代谢影响的生物信息学分析

Bioinformatics Analysis of the Effect of Parent Hyperglycemia on Lipid Metabolism in Offspring

本研究通过腹腔注射链脲佐菌素(STZ,35 mg/kg)或等体积柠檬酸盐缓冲液(CB)建立糖尿病SD雄鼠模型,造模成功后与健康SD雌鼠交配产下子一代(STZ-O)和(CB-O)。取STZ-O和CB-O肝脏组织检测基因表达谱,探讨父代高血糖对后代肝脏脂质代谢的可能调控机制。首先,我们鉴定了(STZ-O)和(CB-O)相比差异表达的基因(differentially expressed genes,DEGs),并构建了蛋白-蛋白互作网络(protein protein interaction network,PPI network)。然后对DEGs进行富集分析(gene ontology,GO)和通路富集分析(kyoto encyclopedia of genes and genomes,KEGG)。最终选择rno04931(Insulin resistance)和rno04932(non-alcohol fatty liver disease(NAFLD))两条通路进行进一步分析,选取交叉基因11个,进行GO功能注释。基于这些基因的GO项,计算出每个基因的潜在重要得分。PPARa和NFKB1的评分明显高于其他基因,说明Ppara和NFKB1可能在rno04931(Insulin resistance)和rno04932(non-alcohol fatty liver disease(NAFLD))两条通路的互扰中发挥重要作用。研究结果说明肝脏基因组表达差异可能是父代高血糖影响子代肝脏代谢功能的调控机制之一。

In this study,we established a diabetic SD male rat model by intraperitoneal injection of streptozotocin(STZ,35 mg/kg)or equal volume citrate buffer(CB),and successfully mated with healthy SD females to produce offspring(STZ-O)and(CB-O).STZ-O and CB-O liver tissues were used to detect gene expression profiles to explore the possible regulatory mechanism of hyperglycemia in offspring.First,we identified differentially expressed genes(DEGs)in the liver of diabetes offspring rats(STZ-O)compared with the normal offspring rats(CB-O)and protein-protein interaction network was constructed.Then,Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were implemented for DEGs.Pathways crosstalk analysis was carried out and we finally selected rno04931(Insulin resistance)and rno04932(Non-alcoholic fatty liver disease(NAFLD))for further analysis.11 genes in intersection of rno04931(Insulin resistance)and rno04932(Non-alcoholic fatty liver disease(NAFLD))were selected and GO functions annotation were carried out.Based on the GO terms of these genes,calculate potential important scores for each gene.The score of Ppara and NFKB1 were significant higher than other genes which indicated that may play important roles in the crosstalk between rno04931(Insulin resistance)and rno04932(Non-alcoholic fatty liver disease(NAFLD)).The results of this study suggest that the difference of liver genome expression in diabetes offspring rats may be one of the regulatory mechanisms for the effect of hyperglycemia on the metabolic function of offspring.