Medical School, Hunan University of Chinese Medicine, Changsha, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha, China.
Front Immunol. 2024 Aug 8;15:1454116. doi: 10.3389/fimmu.2024.1454116. eCollection 2024.
This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia.
Astrocyte-derived exosomes were studied for treating cerebral ischemia in both and models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT‒PCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis protein expression.
Our findings demonstrated that astrocyte-derived exosomes were internalized by neurons both and . Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect.
Astrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis.
本研究旨在探讨星形胶质细胞衍生的外泌体及其 microRNAs（miRNAs）在调节脑缺血时神经元细胞焦亡中的调控作用。
在 和 模型中研究了星形胶质细胞衍生的外泌体治疗脑缺血的作用。通过分析外泌体摄取、神经损伤和焦亡蛋白表达，研究星形胶质细胞衍生的外泌体对神经炎症的影响。使用高通量测序鉴定与焦亡相关的星形胶质细胞衍生的外泌体 miRNA，然后通过 qRT-PCR 进行验证。使用双荧光素酶报告基因测定研究这些 miRNA 与 NLRP3 之间的关系。本研究使用 miR-378a-5p 过表达和敲低来操纵神经细胞的 OGD 损伤。通过分析神经损伤和焦亡蛋白表达，评估星形胶质细胞衍生的外泌体 miR-378a-5p 对调节脑缺血神经炎症的影响。
我们的研究结果表明，星形胶质细胞衍生的外泌体被神经元摄取，并且 和 。此外，星形胶质细胞衍生的外泌体对 OGD 诱导的神经元损伤和大脑中动脉闭塞（MCAO）大鼠缺血皮质区的脑损伤具有神经保护作用，同时减少焦亡。进一步的研究表明，星形胶质细胞衍生的外泌体 miR-378a-5p 通过抑制 NLRP3 参与调节焦亡。miR-378a-5p 的过表达减轻了神经元损伤，而 miR-378a-5p 的敲低增加了 NLRP3 的表达并加剧了焦亡，从而逆转了这种神经保护作用。
星形胶质细胞衍生的外泌体 miR-378a-5p 通过抑制与 NLRP3 介导的细胞焦亡相关的神经炎症对脑缺血具有神经保护作用。需要进一步研究来全面阐明星形胶质细胞衍生的外泌体 miR-378a-5p 调节神经元细胞焦亡的信号通路。
