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基于RNA-seq技术探讨硫酸多糖JCS1S2治疗氧诱导视网膜病变相关机制

白杨 王瑞 王秋元 丁侃 蔡善君

遵义医科大学学报2025,Vol.48Issue(3):243-251,9.
遵义医科大学学报2025,Vol.48Issue(3):243-251,9.

基于RNA-seq技术探讨硫酸多糖JCS1S2治疗氧诱导视网膜病变相关机制

Exploring the mechanisms related to the treatment of oxygen-induced retinopa-thy by sulfated polysaccharide JCS1 S2 based on RNA-seq technology

白杨 1王瑞 1王秋元 1丁侃 2蔡善君1

作者信息

  • 1. 遵义医科大学附属医院 眼科,贵州 遵义 563000
  • 2. 中国科学院CAS 上海药物研究所受体研究重点实验室,上海 201203
  • 折叠

摘要

Abstract

Objective High throughput transcriptome sequencing(RNA-seq)was used to detect the changes of gene expression in eyeball tissue of rats with oxygen-induced retinopathy(OIR),to explore the possible mecha-nism of sulfated polysaccharide JCS1 S2 treatment,and to construct a relative hypoxic cell model to verify the pathway.Methods 27 SD suckling rats were randomly divided into three groups,normal control group,OIR group,and OIR+JCS1 S2 group,with 9 rats each,OIR+JCS1 S2 group received intravitreal injection 4 μl(0.08 mg)JCS1 S2.Rats were euthanized on day 17 and eyeball was stained with hematoxylin eosin(HE)and retinal flat-mount preparation analyzed.RNA-seq was used to screen genes and related pathways involved in OIR pathogenesis.Target proteins were screened in vitro to verify the pathways.Results Morphological observation showed that compared with the normal control group,a large number of vascular endothelial nuclei broke through the inner boundary membrane and the area of non-perfusion area increased in OIR group,while only a small number of vascular endothelial nuclei were found in OIR group treated with JCS1 S2(P<0.05).Transcriptome sequencing results showed that vascular smooth muscle contraction was activated by up-regulation and down-regu-lation of related genes,neuroactive ligand-receptor interaction,and significant expression of drug metabolic path-way,Toll and IMD signal pathways,suggesting that JCS1 S2S drug therapy may achieve the purpose of treating diseases by activating these pathways.Constructing a cell model revealed that its mechanism may be related to the inhibition of serum Toll like receptor 4(TLR4),p-NF-κB,and VEGF protein expression.Conclusion JCS1 S2S can reduce the induction of TLR4/p-NF-κB pathway by hypoxia and down-regulate the synthesis and secretion of VEGF,thus delaying or blocking pathological vascular remodeling.

关键词

氧诱导视网膜病变/硫酸多糖JCS1S2/转录组测序/大鼠模型/Müller细胞

Key words

oxygen-induced retinopathy/sulfated polysaccharide JCS1 S2/transcriptome sequencing/rat mod-el/müller cells

分类

临床医学

引用本文复制引用

白杨,王瑞,王秋元,丁侃,蔡善君..基于RNA-seq技术探讨硫酸多糖JCS1S2治疗氧诱导视网膜病变相关机制[J].遵义医科大学学报,2025,48(3):243-251,9.

基金项目

国家自然科学基金资助项目(NO:31871261) (NO:31871261)

贵州省科技支撑计划项目(NO:黔科合支撑[2023]265). (NO:黔科合支撑[2023]265)

遵义医科大学学报

2096-8159

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