南方医科大学学报2018，Vol.38Issue(8)：901-909,9.DOI:10.3969/j.issn.1673-4254.2018.08.01
地塞米松对内毒素诱导的小鼠葡萄膜炎的治疗效果及转录组分析
Retinal transcriptome profile in mice following dexamethasone treatment for endotoxin-induced uveitis
摘要
Abstract
Objective To investigate the changes in retinal transcriptome profile of mice with endotoxin-induced uveitis (EIU) following dexamethasone (DEX) treatment and explore the mechanisms underlying the therapeutic effect of DEX.Methods EIU was induced in BALB/c mice by intravitreal injection of 125 ng lipopolysaccharide (LPS),followed by topical application of DEX (0.1％) eye drops every 4 h for 24 h.The anterior chamber inflammation was examined with a slit lamp and the clinical scores were assessed.The morphological changes in the eyes were assessed at 24 h after LPS injection.The retinas were harvested for analysis of transcriptome profile using the next-generation sequencing (NGS)-based RNA sequencing (RNA-seq),and the expressions of the inflammatory cytokines and the differentially expressed genes (DEGs) were verified using real-time PCR.Results DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6,TNF-α,MCP-1 and ICAM-1 at 24 h after LPS injection.A total of 52 DEGs were identified by RNA-seq.Within these DEGs,37 genes were upregulated and 15 genes were down-regulated in LPS group as compared with DEX+LPS group.No significantly enriched Gene Ontology (GO) terms was noted.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6 up-regulated and 2 down-regulated KEGG pathways.RIG-I-like receptor signaling pathway and several immune-and inflammation-related genes including Ifit1,H2-T24,Mx2 and Eif2ak2 were significantly down regulated by DEX.Verification with RT-PCR yielded results consistent with these findings.Conclusion DEX alleviates LPS-induced inflammatory response in the retina of mice,and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-and inflammation-related genes.关键词
转录组测序/内毒素诱导性葡萄膜炎/RIG-I类受体信号通路/炎症/地塞米松Key words
endotoxin-induced uveitis/dexamethasone/transcriptome/RIG-I-like receptor signaling pathway/inflammation引用本文复制引用
余鹏,邱一果,林茹,符馨予,郝冰涛,雷博..地塞米松对内毒素诱导的小鼠葡萄膜炎的治疗效果及转录组分析[J].南方医科大学学报,2018,38(8):901-909,9.基金项目
国家自然科学基金(81470621,81770949) （81470621,81770949）
河南省科技攻关项目(182102310145) （182102310145）
中国国家重点临床专业建设项目 （）
Supported by National Natural Science Foundation of China (81470621,81770949),Science and Technology Bureau of Henan Province (182102310145),and National Key Clinical Specialties Construction Program of China. （81470621,81770949）
