Zhang Yi, Sun Chang, Wang Bailun, Gu Angran, Zhou Ziyi, Gu Changping
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
CNS Neurosci Ther. 2024 Dec;30(12):e70189. doi: 10.1111/cns.70189.
This study aimed to explore the role and underlying mechanisms of brain-derived exosomes in traumatic brain injury-induced acute lung injury (TBI-induced ALI), with a particular focus on the potential regulation of ferroptosis through miRNAs and Scd1.
To elucidate TBI-induced ALI, we used a TBI mouse model. Exosomes were isolated from the brains of these mice and characterized using TEM and NTA. LC-MS analysis revealed an increase in the level of ferroptosis in the lung tissues of mice with TBI. Subsequent miRNA and mRNA sequencing revealed the upregulation of miR-9-5p and the downregulation of Scd1 in the pulmonary tissues of these mice. Ferroptosis was assessed by quantifying the levels of ROS, MDA, and Fe and the expression of proteins associated with ferroptosis.
TBI led to the release of exosomes enriched with miR-9-5p, which targeted Scd1 in lung tissue, thereby promoting ferroptosis. Treatment with antagomir 9-5p reduced the level of ALI in TBI mice, indicating that exosomal miR-9-5p plays a significant role in TBI-induced ALI.
This study revealed that brain-derived exosomal miR-9-5p mediates ferroptosis in TBI-induced ALI by targeting Scd1. These findings may provide new insights into the complex interplay between TBI and ALI and highlight the potential of miR-9-5p as a target for the development of novel therapeutic strategies.
本研究旨在探讨脑源性外泌体在创伤性脑损伤诱导的急性肺损伤（TBI 诱导的 ALI）中的作用及潜在机制，特别关注通过微小 RNA（miRNA）和硬脂酰辅酶 A 去饱和酶 1（Scd1）对铁死亡的潜在调控。
为阐明 TBI 诱导的 ALI，我们使用了 TBI 小鼠模型。从这些小鼠的脑中分离出外泌体，并通过透射电子显微镜（TEM）和纳米颗粒跟踪分析（NTA）进行表征。液相色谱 - 质谱（LC - MS）分析显示，TBI 小鼠肺组织中铁死亡水平升高。随后的 miRNA 和 mRNA 测序显示，这些小鼠肺组织中 miR - 9 - 5p 上调，Scd1 下调。通过定量活性氧（ROS）、丙二醛（MDA）和铁的水平以及与铁死亡相关的蛋白质表达来评估铁死亡。
TBI 导致富含 miR - 9 - 5p 的外泌体释放，其靶向肺组织中的 Scd1，从而促进铁死亡。用抗 miR - 9 - 5p 处理可降低 TBI 小鼠的 ALI 水平，表明外泌体 miR - 9 - 5p 在 TBI 诱导的 ALI 中起重要作用。
本研究表明，脑源性外泌体 miR - 9 - 5p 通过靶向 Scd1 介导 TBI 诱导的 ALI 中的铁死亡。这些发现可能为 TBI 和 ALI 之间的复杂相互作用提供新的见解，并突出 miR - 9 - 5p 作为新型治疗策略开发靶点的潜力。
