[1]余鹏,邱一果,林茹,等.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,(08):901.
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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()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
901
栏目:
出版日期:
2018-07-31

文章信息/Info

Title:
Retinal transcriptome profile in mice following dexamethasone treatment for endotoxin-induced uveitis
作者:
余鹏邱一果林茹符馨予郝冰涛雷博
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
Keywords:
endotoxin-induced uveitis dexamethasone transcriptome RIG-I-like receptor signaling pathway inflammation
摘要:
目的研究地塞米松(DEX)对内毒素诱导性葡萄膜炎(EIU)的治疗效果及转录组测序探讨其潜在的机制。方法将125 ng 脂多糖( LPS) 注射入雌性BALB/c小鼠玻璃体内建立EIU模型,每隔4 h用0.1% DEX滴眼,共6次。注射LPS后24 h 用裂隙 灯观察小鼠眼前房炎症情况并进行临床评分。苏木精-伊红染色法观察小鼠眼部形态学变化。RNA-seq对EIU模型组和DEX 治疗组小鼠的视网膜进行转录组测序并进行GO和KEGG功能分析。Real-time PCR检测小鼠视网膜炎症细胞因子表达及验证 选出的差异基因。结果连续滴眼6次后,DEX可减轻EIU前房的炎症,并下调炎症因子白介素-6(IL-6)、肿瘤坏死因子-α(TNF- α)、单核细胞趋化蛋白-1(MCP-1)和细胞间黏附分子-1(ICAM-1)mRNA的表达。RNA-seq共检测出52个差异基因,与DEX+ LPS组相比,LPS组中上调的基因有37个,下调的基因有15个。差异基因的功能分析未发现显著富集的GO条目。KEGG富集 分析显示有6个显著上调的KEGG通路和2个显著下调的KEGG通路。KEGG结果提示DEX治疗后可下调RIG-I类受体信号 通路(Ddx58、Ifih1和Isg15)及一些免疫炎症相关基因(Ifit1、H2-T24、Mx2和Eif2ak2)。结论DEX对LPS 引起的小鼠内毒素 诱导性小鼠葡萄膜炎有保护作用,此保护作用可能与下调RIG-I类受体信号通路及一些免疫炎症相关基因有关。
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.
更新日期/Last Update: 1900-01-01