米诺环素通过激活 Nrf2/Hmox1 通路防止铁死亡和减轻急性间隔综合征的机制。
Mechanism of minocycline activating Nrf2/Hmox1 pathway to prevent ferroptosis and alleviate acute compartment syndrome.
机构信息
Department of Orthopedics Trauma and Hand Surgery, the First Affiliated Hospital of Guangxi Medical University, NO.6 ShuangYong Road, Nanning, Guangxi, 530022, China.
Department of Orthopedic Trauma, The Affiliated Changsha Central Hospital (Changsha Central Hospital), Hengyang Medical School, University of South China, Changsha, Hunan, 410004, China.
出版信息
J Orthop Surg Res. 2024 Oct 24;19(1):686. doi: 10.1186/s13018-024-05183-z.
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.
背景
急性间隔综合征（ACS）是创伤的一种危险后果。ACS 的确切病因尚不清楚。我们进行了研究，以证实通过抑制铁死亡和激活 Nrf2/Hmox1 通路可以缓解急性间隔综合征。
方法
我们建立了 ACS 大鼠模型，并对骨骼肌组织进行了下一代测序（NGS），以鉴定差异表达的靶基因。最终，我们进行了体内实验，以验证 ACS 大鼠中是否存在铁死亡和 Nrf2/Hmox1 通路。米诺环素干预后，通过检查与铁死亡相关的变化，评估药物对 ACS 的影响。
结果
生物信息学分析表明，疾病中的遗传变化主要集中在铁死亡上，Nrf2/Hmox1 有明显改变。基于体内结果，观察到 ACS 大鼠的铁死亡水平明显高于对照组大鼠。米诺环素抑制 Nrf2/Hmox1 通路可改善 ACS 结局，并减少干预后的组织损伤。
结论
米诺环素通过刺激 Nrf2/Hmox1 通路抑制铁死亡，从而减缓急性间隔综合征的进展。
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