{"title":"Dl-3-n-butylphthalein inhibits neuronal apoptosis and ferroptosis after cerebral ischemia-reperfusion injury in rats by regulating CXCR4.","authors":"Sifan Xu, Qi Wang, Yu Qin, Qian Yang, Yang Xu, Zhiming Zhou","doi":"10.1016/j.ntt.2025.107434","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the anti-apoptosis and anti-ferroptosis effects of dl-3-n-butylphthalide (dl-NBP) on cerebral ischemia-reperfusion injury (CIRI) in rats, and the potential involvement of cysteine-X-cysteine chemokine receptor 4 (CXCR4).</p><p><strong>Methods: </strong>The differentially expressed genes between healthy people and stroke patients were screened by GEO database. A transient middle cerebral artery occlusion rat model was used to induce CIRI in vivo. Rats were randomly divided into sham group, tMCAO group, and dl-NBP + tMCAO group. The therapeutic effect of dl-NBP in vivo and its effect on apoptosis and ferroptosis in brain tissues were evaluated. An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to simulate CIRI in cultured PC12 cells, and the effects of dl-NBP on apoptosis and ferroptosis were examined. In this model, CXCR4 expression was assessed by western blotting and its involvement in dl-NBP-mediated protection assessed by inhibition with AMD3100.</p><p><strong>Results: </strong>In the stroke-related GSE22255 and GSE66724 datasets, a total of six genes with increased co-expression were found, including CXCR4. Dl-NBP treatment significantly reduced both the volume of cerebral infarction and the degree of cerebral edema, and improved neurological function in rats. dl-NBP reduced the degree of apoptosis and ferroptosis and alleviated CIRI both in vivo and in vitro. The pro-survival effects of dl-NBP were significantly reversed after CXCR4 inhibition with AMD3100.</p><p><strong>Conclusion: </strong>Dl-NBP has anti-apoptotic and anti-ferroptotic effects on CIRI both in vivo and in vitro, and this effect is mediated by CXCR4.</p>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":" ","pages":"107434"},"PeriodicalIF":2.6000,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotoxicology and teratology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ntt.2025.107434","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To investigate the anti-apoptosis and anti-ferroptosis effects of dl-3-n-butylphthalide (dl-NBP) on cerebral ischemia-reperfusion injury (CIRI) in rats, and the potential involvement of cysteine-X-cysteine chemokine receptor 4 (CXCR4).
Methods: The differentially expressed genes between healthy people and stroke patients were screened by GEO database. A transient middle cerebral artery occlusion rat model was used to induce CIRI in vivo. Rats were randomly divided into sham group, tMCAO group, and dl-NBP + tMCAO group. The therapeutic effect of dl-NBP in vivo and its effect on apoptosis and ferroptosis in brain tissues were evaluated. An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to simulate CIRI in cultured PC12 cells, and the effects of dl-NBP on apoptosis and ferroptosis were examined. In this model, CXCR4 expression was assessed by western blotting and its involvement in dl-NBP-mediated protection assessed by inhibition with AMD3100.
Results: In the stroke-related GSE22255 and GSE66724 datasets, a total of six genes with increased co-expression were found, including CXCR4. Dl-NBP treatment significantly reduced both the volume of cerebral infarction and the degree of cerebral edema, and improved neurological function in rats. dl-NBP reduced the degree of apoptosis and ferroptosis and alleviated CIRI both in vivo and in vitro. The pro-survival effects of dl-NBP were significantly reversed after CXCR4 inhibition with AMD3100.
Conclusion: Dl-NBP has anti-apoptotic and anti-ferroptotic effects on CIRI both in vivo and in vitro, and this effect is mediated by CXCR4.
期刊介绍：
Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.
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