中国中医眼科杂志2025，Vol.35Issue(10)：907-915,9.DOI:10.13444/j.cnki.zgzyykzz.2025.10.002
基于网络药理学及实验验证探讨固本清目方治疗年龄相关性黄斑变性的机制
Mechanisms of Guben Qingmu Formula in the Treatment of Age-related Macular Degeneration Based on Network Pharmacology and Ex-perimental Validation
摘要
Abstract
OBJECTIVE To explore the mechanisms of Guben Qingmu Formula(GBQM)in the treatment of age-related macular degeneration(AMD)using network pharmacology and experimental validation.METHODS The active compounds of GBQM were screened from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and relevant literature.Protein-protein interaction(PPI)network analysis was conducted to identify core targets,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target-pathway network was constructed,and molecular docking was performed for validation.An in vitro oxidative stress model of retinal pigment epithelial(RPE)cell was established by sodium iodate induction.Cells were divided into control group(CG),model group(MG),blank serum group(BS),5%low-concentration GBQM group(L-GBQM),and 10%high-concentration GBQM group(H-GBQM).After 24 h intervention,cytotoxicity was assessed by lactate dehydrogenase(LDH)release assay;Superoxide dismutase(SOD)and reactive oxygen species(ROS)levels were measured by protein quantification kit and immunofluorescence,respectively;Interleukin-1β(IL-1β),interleukin-10(IL-10),and interferon-γ(IFN-γ)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of protein kinase B1(AKT1),epidermal growth factor receptor(EGFR),B-cell lymphoma-2(BCL-2),signal transducer and activator of transcription 3(STAT3),and hypoxia-inducible factor-1α(HIF-1α)at both mRNA(qRT-PCR)and protein(Western Blot)levels was analyzed.RESULTS(1)Network pharmacology:A total of 40 active compounds of GBQM and 243 intersecting targets related to AMD were identified.PPI network analysis yielded 10 core targets.GO enrichment suggested that GBQM intervention in AMD may be associated with oxidative stress,while KEGG enrichment indicated involvement of multiple signaling pathways,including HIF-1.Molecular docking demonstrated favorable binding activity between GBQM compounds and six target proteins(AKT1,TNF,EGFR,BCL-2,STAT3,HIF-1).(2)Cytotoxicity:LDH levels were higher in MG than in CG,but significantly reduced in L-GBQM and H-GBQM compared with MG and BS(all P<0.05).(3)SOD and ROS:SOD expression was decreased and ROS increased in MG compared with CG.L-GBQM and H-GBQM increased SOD and reduced ROS compared with MG and BS(all P<0.05).(4)Inflammatory cytokines:IL-10,IL-1β,and IFN-γ were elevated in MG compared with CG,whereas reduced in BS,L-GBQM,and H-GBQM groups compared with MG.Furthermore,IL-10 and IL-1β were lower in L-GBQM and H-GBQM than in BS,and IFN-γ was reduced in H-GBQM compared with BS(all P<0.05).(5)mRNA and protein expression:AKT1,EGFR,STAT3,and HIF-1α were upregulated,while BCL-2 was downregulated in MG compared with CG.L-GBQM and H-GBQM downregulated AKT1,EGFR,STAT3,and HIF-1α,and upregulated BCL-2 compared with MG and BS(all P<0.05).CONCLUSIONS GBQM exerts therapeutic effects on AMD by attenuating pathological damage in oxidative stress-induced RPE cells.Its mechanism may involve multiple compounds,targets,and pathways,particularly modulation of oxidative stress and regulation of signaling molecules such as HIF-1α.关键词
固本清目方/年龄相关性黄斑变性/网络药理学/实验验证Key words
Guben Qingmu Formula/age-related macular degeneration/network pharmacol-ogy/experimental validation分类
医药卫生引用本文复制引用
莫亚欣,刘新宇,李佳贤,陈鑫,孙雪,陈强..基于网络药理学及实验验证探讨固本清目方治疗年龄相关性黄斑变性的机制[J].中国中医眼科杂志,2025,35(10):907-915,9.基金项目
1中国中医科学院眼科医院高水平中医医院课题(GSP5-32)2中国中医科学院眼科医院横向课题(101120351) （GSP5-32）
