Retinal Transcriptome Analysis in the Treatment of Endotoxin-Induced Uveitis with Tetramethylpyrazine Eye Drops
Retinal Transcriptome Analysis in the Treatment of Endotoxin-Induced Uveitis with Tetramethylpyrazine Eye Drops
复制标题
川芎嗪滴眼液治疗内毒素引起的葡萄膜炎的视网膜转录组分析
DOI：
10.1089/jop.2018.0105
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发表时间：
2019-04-17
影响因子：
2.3
通讯作者：
Lei, Bo
中科院分区：
文献类型：
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作者：
Yang, Lin;Qiu, Yiguo;Lei, Bo
目的：目的观察川芎嗪滴眼液对内毒素性葡萄膜炎（EIU）小鼠视网膜基因表达的影响，并探讨其作用机制。方法：对眼前节的炎症体征进行评估，并进行临床评分。通过RNA测序（RNA-seq）策略鉴定来自TMP滴眼液处理的和未处理的小鼠的视网膜转录组。差异表达基因（DEG）通过实时PCR验证。使用STRING软件分析蛋白质-蛋白质相互作用。结果如下：与TMP治疗组相比，未治疗对照组在脂多糖给药后24 h炎症反应明显加重，临床评分显著升高（P < 0.001）。RNA-seq分析鉴定了407个DEG，其中356个上调，51个下调。有12个上调的基因本体论术语丰富和27个上调的途径。七个DEG，包括炎症相关的，补体系统相关的，和干扰素相关的基因，使用定量PCR验证。结论：川芎嗪对EIU有抗炎作用。局部应用TMP可通过调节炎症相关基因抑制视网膜炎症反应，提示TMP可能是一种潜在的眼部炎症治疗药物。
Purpose: To investigate retinal gene expression of tetramethylpyrazine (TMP) eye drop-treated endotoxin-induced uveitis (EIU) in mice and to explore the mechanisms. Methods: The inflammatory signs of the anterior segment were evaluated, and clinical scores were graded. The retinal transcriptome from the TMP eye drop-treated and the untreated mice was identified by RNA sequencing (RNA-seq) strategy. Differentially expressed genes (DEGs) were validated by real-time PCR. The protein-protein interaction was analyzed using the STRING software. Results: Compared with the TMP-treated group, the inflammatory responses of the untreated control group were much severe and clinical score was remarkably higher (P < 0.001) at 24 h after lipopolysaccharide administration. RNA-seq assay identified 407 DEGs, among which 356 were upregulated and 51 were downregulated. There were 12 upregulated gene ontology terms enriched and 27 upregulated pathways. Seven DEGs, including inflammation-related, complement system-related, and interferon-related genes, were validated using quantitative PCR. Conclusions: TMP exerted anti-inflammatory effect in EIU. Local application of TMP inhibited retinal inflammatory response by regulating the inflammation-related genes, suggesting that TMP may be a potential novel therapeutic drug for ocular inflammation.