Exploring the mechanisms of Hexue Mingmu Tablets in improving diabetic retinopathy of zebrafish based on transcriptomics
10.3980/j.issn.1672-5123.2025.7.02
- VernacularTitle: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
- Author:
Duo ZHAO
1
,
2
,
3
;
Zilu ZHU
1
,
2
,
3
;
Peng DUAN
1
,
2
,
3
;
Jiaolong HUANG
1
,
2
,
3
;
Meijuan ZHU
1
,
2
,
3
;
Min ZHANG
1
,
2
,
3
Author Information
1. Xiangyang No.1 People's Hospital Affiliated to Hubei University of Medicine
2. Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Xiangyang City, Xiangyang 441000, Hubei Province, China
3. Hubei University of Medicine, Shiyan 442000, Hubei Province, China
- Publication Type:Journal Article
- Keywords:
transcriptomics;
Hexue Mingmu Tablets;
diabetic retinopathy;
zebrafish
- From:
International Eye Science
2025;25(7):1046-1055
- CountryChina
- Language:Chinese
-
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.
