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川芎嗪滴眼液治疗内毒素诱导性葡萄膜炎的视网膜转录组分析

Retinal Transcriptome Analysis in the Treatment of Endotoxin-Induced Uveitis with Tetramethylpyrazine Eye Drops.

作者信息

Yang Lin, Qiu Yiguo, Liu Jingyang, Lin Ru, Yu Peng, Fu Xinyu, Hao Bingtao, Lei Bo

机构信息

1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

2 People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Henan Eye Institute, Henan Eye Hospital, Zhengzhou, China.

出版信息

J Ocul Pharmacol Ther. 2019 May;35(4):235-244. doi: 10.1089/jop.2018.0105. Epub 2019 Apr 17.

Abstract

To investigate retinal gene expression of tetramethylpyrazine (TMP) eye drop-treated endotoxin-induced uveitis (EIU) in mice and to explore the mechanisms. 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. Compared with the TMP-treated group, the inflammatory responses of the untreated control group were much severe and clinical score was remarkably higher ( < 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. 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.

摘要

研究川芎嗪(TMP)滴眼液治疗小鼠内毒素诱导性葡萄膜炎(EIU)的视网膜基因表达并探讨其机制。评估眼前节的炎症体征并对临床评分进行分级。采用RNA测序(RNA-seq)策略鉴定TMP滴眼液治疗组和未治疗组小鼠的视网膜转录组。通过实时PCR验证差异表达基因(DEG)。使用STRING软件分析蛋白质-蛋白质相互作用。与TMP治疗组相比,未治疗的对照组在给予脂多糖后24小时的炎症反应更为严重,临床评分显著更高(<0.001)。RNA-seq分析鉴定出407个DEG,其中356个上调,51个下调。有12个上调的基因本体术语富集和27条上调的通路。使用定量PCR验证了7个DEG,包括炎症相关、补体系统相关和干扰素相关基因。TMP在EIU中发挥抗炎作用。局部应用TMP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新型治疗药物。

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