高脂血症长爪沙鼠模型的转录组检测和代谢性炎症通路的初步研究

Detection of transcriptome in hyperlipidemia and metabolic/inflammatory pathways in Mongolian gerbils

目的研究饮食诱发的高脂血症长爪沙鼠模型的关键基因及代谢性炎症通路调控网络。方法利用RNA-Seq测序技术及生物信息学技术对正常组与模型组两个RNA池进行测序和分析。结果 De novo拼接后获得有效长爪沙鼠基因47 522个(即≥100 bp的unigene),大小26.9 Mb,与GenBank中现有的基因比对结果表明,约82.53%的序列与基因组上的外显子序列同源;诱发高脂血症动物与正常动物之间共获得21 125个差异基因,其中16 087个下调,5 038个上调,模型组相对于正常组存在显著的下调关系(P<0.01)。其中与长爪沙鼠高脂血症代谢性炎症密切相关的通路有8个(P<0.01),这8个通路所表达的基因中有15个与免疫和炎症相关的基因显著下调(P<0.01)。结论 RNA-Seq测序和生物信息技术可作为研究高脂血症动物模型的整体基因转录的工具,筛选出的关键基因和通路可作为研究的候选基因或操作靶点。

Objective To understand some key genes and metabolic/inflammatory pathways triggered by high fat/high cholesterol （ HF/HC ） diet-induced hyperlipidemia in Mongolian gerbil .Methods Sixty 90-day-old Mongolian gerbils （including both sexes） were used in this study.The gerbils were divided into normal group （n=30, control diets） and model group （n=30, Hf/HC diets）.Hyperlipidemia was induced for 4 weeks.To extract mRNA for transcriptome by RNA-Seq deep sequencing and bioinformatics .Results The results showed that 47 522 de novo gerbil genes （≥100 bp unigene ） were obtained , with a total of 26.9 Mb, and about 82.53% sequence was homologous with the exon in the common genome bases .There were 21 125 differential genes between the hyperlipidemia gerbil and normal gerbil groups , including 16 087 down-regulated and 5038 up-regulated genes .There was a significant trend of downregulation compared with the normal group （ P 〈0.01 ） .There were eight pathways significantly related to the metabolic inflammation in hyperlipidemia （ P〈0.01） , and among the expressed genes of these pathways , 15 immune-and inflammation-related genes were significantly down-regulated （ P〈0.01 ） .Conclusions RNA-Seq and bioinformatics techniques can be used as a powerful tool for overall gene-transcription in hyperlipidemic gerbil models .Some key genes and pathways screened in this study may become candidate genes or operating targets in the future research .