海南医学院学报2024，Vol.30Issue(22)：1717-1726,10.DOI:10.13210/j.cnki.jhmu.20240709.002
通窍明目汤调控p53/SLC7A11介导的氧化损伤及铁死亡改善青光眼RGC损伤的作用机制
The mechanism of Tongqiao Mingmu Decoction regulating p53/SLC7A11 mediated oxidative damage and ferroptosis in improving RGC damage in glaucoma
摘要
Abstract
Objective:To explore the molecular mechanism of Tongqiao Mingmu Decoction in improving optic nerve damage in glaucoma.Method:Using network pharmacology methods,drug,disease,and ferroptosis database targets were searched,com-mon and key targets were screened,and a"Tongqiao Mingmu Decoction-glaucoma-ferroptosis"network was constructed,fol-lowed by pathway enrichment analysis;In vitro experiments induced RGC with hydrogen peroxide.After successful modeling,the mice were randomly divided into three groups:model group,Tongqiao Mingmu Decoction group,and positive drug group.A nor-mal blank group was also set up,and Tongqiao Mingmu Decoction(99.96 g/kg)was administered by gavage intervention starting from week 5.After the experiment,CCK-8 was used to detect RGC proliferation,and flow cytometry was used to detect ROS ex-pression.ELISA was used to detect the content and activity of iron ions,MDA,SOD,GSH-PX in RGC.Western blot was used to detect the expression changes of ACSL4,GPX-4,FTH-1 proteins and p53/SLC7A11 related proteins in RGC,and RT-PCR was used to detect the mRNA content of p53 and SLC7A11 in RGC.Result:After intervention with Tongqiao Mingmu Decoc-tion,compared with the model group,Tongqiao Mingmu Decoction significantly reduced the positive rate of reactive oxygen spe-cies,iron ion levels,and MDA content in RGC,downregulated the expression of p53,ACSL4,ACSL4,and p53 mRNA in RGC nucleus,increased RGC proliferation rate,increased SOD,CAT,and GSH levels,and upregulated the expression of GPX-4,FTH-1,SLC7A11,GPX-4,FTH-1,and SLC7A11 mRNA(P<0.05).Conclusion:Tongqiao Mingmu Decoction may in-volve multiple molecular pathways through multiple components and targets,and its mechanism may be related to blocking the ex-pression of intracellular p53 in the p53/SLC7A11 signaling pathway and the RGC ferroptosis mediated by system Xc-,inhibiting the expression of SLC7A11,leading to a decrease in cysteine,increasing ferroptosis sensitivity,triggering oxidative stress and ex-cessive inflammatory response,thereby avoiding cell damage and functional disorders.关键词
通窍明目汤/视网膜神经节细胞/氧化应激损伤/铁死亡/p53/SLC7A11信号通路Key words
Tongqiao Mingmu Decoction/RGC/Oxidative stress injury/Ferroptosis/p53/SLC7A11 signaling pathway分类
医药卫生引用本文复制引用
杨稀瑞,王继雪,王思琦,孙会兰,袁星星,孙河..通窍明目汤调控p53/SLC7A11介导的氧化损伤及铁死亡改善青光眼RGC损伤的作用机制[J].海南医学院学报,2024,30(22):1717-1726,10.基金项目
This study was supported by National Natural Science Foundation of China Youth Fund Project(82205195,82205117) （82205195,82205117）
Research Special Project of Henan Provincial Clinical Research Base of Traditional Chinese Medicine(2022JDZX127,2022JDZX135) （2022JDZX127,2022JDZX135）
Henan Province Medical Science and Technology Research Program Project(LHGJ20230686) 国家自然科学基金青年基金项目(82205195,82205117) （LHGJ20230686）
河南省中医临床研究基地科研专项(2022JDZX127,2022JDZX135) （2022JDZX127,2022JDZX135）
河南省医学科技攻关计划项目(LHGJ20230686) （LHGJ20230686）
