神经药理学报2024，Vol.14Issue(6)：1-12,12.DOI:10.3969/j.issn.2095-1396.2024.06.001
基于网络药理学和分子对接探讨牛磺酸治疗年龄相关性黄斑病变的机制
To Investigate the Mechanism of Taurine for Age-Related Macular Degeneration Based on Network Pharmacology and Molecular Docking
摘要
Abstract
Objective:To investigate the effect and mechanism of Taurine in the treatment of age-related macular degeneration(AMD)by using network pharmacology and molecular docking technology and in vitro experiments.Methods:The intersection targets of Taurine and AMD were obtained and screened from different databases.Through the Protein Interaction Network(PPI).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG Enrichment Analysis)signal pathway analysis,according to Cytoscape to establish a"drug-target-pathway"network to deeply explore the mechanism of Taurine action on AMD.Preliminary verification by molecular docking technology.The model of ARPE-19 cell senescence was established by H2O2 in vitro.Cell proliferation assay kit(CCK-8)was used to detect the optimal concentration and action time of H2O2 and Taurine.The senescence degree was detected by β-galactosidase kit staining.The levels of steroid receptor co-activating protein(SRC),tumor protein 53(P53),and myeloperoxidase(MPO)were detected by Western blotting(WB)assay.The expression levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by ELISA kit.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to analyze the expression levels of target genes SRC,P53 and MPO mRNA.Results:Network pharmacological analysis showed that the intersection of Taurine and AMD targets included inflammation-related factors such as SRC,IL-6,TNF-α,and cell senescence related targets such as P53 and MPO.The results of GO biological function and KEGG pathway enrichment analysis show that it contains signaling pathways related to aging inflammation.The results of β-galactosidase staining and CCK-8 experiment showed that the optimal concentration of H2O2 on APRE-19 cells was 100μmol·L-1 for 24 h,and Taurine 10 mmol·L-1,20 mmol·L-1 and 40 mmol·L-1 were suitable concentrations.WB results showed that SRC was significantly increased and P53 and MPO were significantly decreased in Taurine group compared with model group.PCR results showed that compared with the model group,mRNA level of SRC was significantly increased,and P53 and MPO mRNA levels were significantly decreased in Taurine group.ELISA results showed that IL-6 and TNF-α were significantly decreased in Taurine group compared with model group.Conclusion:Network pharmacology,molecular docking and cell experiments were used to confirm that Taurine has an anti-aging effect on ARPE-19 cells by inhibiting inflammation through the SRC-P53-MPO axis.It provides a scientific basis for further elucidation of the mechanism of action of taurine in the treatment of AMD.关键词
牛磺酸/年龄相关性黄斑病变/分子对接/网络药理学/P53靶点Key words
Taurine/age-related macular degeneration/molecular docking/network pharmacology分类
医药卫生引用本文复制引用
陈晓阳,陈茁茁,张元元,于嘉琛,杨志强,王子祎,谢亚昊,靳琪,刘思宁,安佳怡,刘亚萌,强孟泽,李家赓..基于网络药理学和分子对接探讨牛磺酸治疗年龄相关性黄斑病变的机制[J].神经药理学报,2024,14(6):1-12,12.基金项目
河北省教育厅青年基金项目(No.JYT2024021),2023年大学生创新创业训练项目(No.202310092006),河北北方学院校级项目(No.XJ2021028),河北省卫生厅项目(No.20200487),河北省自然科学基金资助项目(No.2023405003) （No.JYT2024021）
