国际眼科杂志2025，Vol.25Issue(7)：1046-1055,10.DOI:10.3980/j.issn.1672-5123.2025.7.02
基于转录组学探讨和血明目片改善斑马鱼糖尿病视网膜病变的作用机制
Exploring the mechanisms of Hexue Mingmu Tablets in improving diabetic retinopathy of zebrafish based on transcriptomics
摘要
Abstract
AIM:To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics. METHODS:Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf).Larvae were randomized into four groups:control group(CG;aquaculture water),model group(MG;130 mmol/L glucose),low-dose HXMMT treatment group(L-HX;130 mmol/L glucose+7.5 mg/L HXMMT),and high-dose HXMMT treatment group(H-HX;130 mmol/L glucose+75 mg/L HXMMT),with a 3-day intervention period until 6 dpf.The area and length of eyes,and body length of zebrafish were observed by stereomicroscopy,retinal morphology was observed by hematoxylin-eosin staining(HE),and retinal vessel diameter was observed under fluorescence microscope.Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish,and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR). RESULTS:HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement,widened gaps,and thickened inner nuclear layer(INL)in ganglion cell layer GCL);retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG,and it was significantly changed after the intervention of HXMMT,with significant efficacy in the H-HX(P＜0.05);transcriptomics profiling identified 1 470 reversed DEGs,predominantly enriched in the AMPK signaling pathway,FoxO signaling pathway,retinal developmental processes,and tight junction regulation.Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571,P＜0.05). CONCLUSION:HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1,pde6c,arr3a,plk1,fbp1b,foxo1a,pcna,and cdk1,as well as synergistically modulating processes such as retinal development in camera-type eyes,visual perception,microtubule cytoskeletal organization,tight junctions,and the AMPK signaling pathway,Foxo signaling pathway.关键词
转录组学/和血明目片/糖尿病视网膜病变/斑马鱼Key words
transcriptomics/Hexue Mingmu Tablets/diabetic retinopathy/zebrafish引用本文复制引用
赵朵,朱紫潞,段鹏,黄娇龙,朱美娟,张敏..基于转录组学探讨和血明目片改善斑马鱼糖尿病视网膜病变的作用机制[J].国际眼科杂志,2025,25(7):1046-1055,10.基金项目
湖北省自然科学基金青年项目(No.2023AFB495,2025AFB527) （No.2023AFB495,2025AFB527）
襄阳市科技局指导项目(No.2022YL48A) Hubei Provincial Natural Science Foundation Youth Project(No.2023AFB495,2025AFB527) （No.2022YL48A）
Xiangyang Science and Technology Bureau Guidance Project(No.2022YL48A) （No.2022YL48A）
