高尿酸血症小鼠肠渗透性增加的差异表达基因分析

DIFFERENTIALLY EXPRESSED GENES FOR INCREASED INTESTINAL PERMEABILITY IN HYPERURICEMIA MICE

目的通过转录组测序技术和生物信息学分析探究引起高尿酸血症小鼠肠渗透性增加的相关基因。方法通过RNA测序分析高尿酸血症和正常小鼠肠组织的差异表达基因,对差异表达基因进行GO功能注释和KEGG通路富集,并通过实时荧光定量PCR(RT-qPCR)进一步对部分差异表达基因进行验证。结果差异表达基因在结肠中有1006个,在回肠中有347个,在空肠中有398个。花生四烯酸代谢信号通路在空肠、回肠和结肠中均被显著富集,特别是细胞色素P450(CYP450)系列相关基因。高尿酸血症小鼠与正常小鼠相比,空肠和结肠中CYP2C55和CYP2E1基因表达差异显著。RT-qPCR验证结果表明,在高尿酸血症小鼠空肠和结肠中CYP2E1表达升高(t=4.717、9.986,P<0.05),CYP2C55表达降低(t=3.682、4.047,P<0.05)。结论高尿酸血症小鼠肠渗透性增加与CYP2E1的表达增高和CYP2C55的表达降低有关,这为高尿酸血症引起肠渗透性增加的机制研究提供了新的思路。

Objective To investigate the genes associated with increased intestinal permeability in hyperuricemia mice through transcriptome sequencing and bioinformatics analysis.Methods RNA sequencing was used to investigate the differen-tially expressed genes in intestinal tissue between hyperuricemia mice and normal mice.GO functional annotation and KEGG pathway enrichment were performed for the differentially expressed genes,and RT-qPCR was used to further validate the differentially expressed genes.Results There were 1006 differentially expressed genes in the colon,347 in the ileum,and 398 in the jejunum.The arachidonic acid metabolic signaling pathway was significantly enriched in the jejunum,ileum,and colon,especially CYP450-related genes.There were significant differences in the expression levels of CYP2C55 and CYP2E1 in the jejunum and the colon between hyperuricemia mice and normal mice.RT-qPCR validation showed a significant increase in the expression of CYP2E1(t=4.717,9.986;P<0.05)and a significant reduction in the expression of CYP2C55(t=3.682,4.047;P<0.05)in the jejunum and the colon of hyperuricemia mice.Conclusion Increased intestinal permeability in hyperuricemia mice is associated with the increase in CYP2E1 and the reduction in CYP2C55,which provides new ideas for the research on the mechanism of increased intestinal permeability caused by hyperuricemia.