Xiong Liao, Zhao Huang, He Ling, Wencai Li, Junjie Liu, Yonghui Lao, Wei Su
{"title":"米诺环素激活 Nrf2/Hmox1 通路防止铁变态反应和缓解急性隔室综合征的机制","authors":"Xiong Liao, Zhao Huang, He Ling, Wencai Li, Junjie Liu, Yonghui Lao, Wei Su","doi":"10.1186/s13018-024-05183-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway.</p><p><strong>Methods: </strong>We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis.</p><p><strong>Results: </strong>The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention.</p><p><strong>Conclusion: </strong>Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"19 1","pages":"686"},"PeriodicalIF":2.8000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515506/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mechanism of minocycline activating Nrf2/Hmox1 pathway to prevent ferroptosis and alleviate acute compartment syndrome.\",\"authors\":\"Xiong Liao, Zhao Huang, He Ling, Wencai Li, Junjie Liu, Yonghui Lao, Wei Su\",\"doi\":\"10.1186/s13018-024-05183-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway.</p><p><strong>Methods: </strong>We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis.</p><p><strong>Results: </strong>The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention.</p><p><strong>Conclusion: </strong>Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome.</p>\",\"PeriodicalId\":16629,\"journal\":{\"name\":\"Journal of Orthopaedic Surgery and Research\",\"volume\":\"19 1\",\"pages\":\"686\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515506/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Orthopaedic Surgery and Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13018-024-05183-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Surgery and Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13018-024-05183-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
Mechanism of minocycline activating Nrf2/Hmox1 pathway to prevent ferroptosis and alleviate acute compartment syndrome.
Background: Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway.
Methods: We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis.
Results: The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention.
Conclusion: Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome.
期刊介绍：
Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues.
Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications.
JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.
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