运动预处理增加脑缺血再灌注损伤大鼠循环外泌体miR-124表达，减轻细胞凋亡。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-01-15 DOI:10.1016/j.brainres.2025.149457

Wenjing Song , Lili Teng , Haoran Wang , Ruifeng Pang , Runyu Liang , Luwen Zhu

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引用次数: 0

摘要

目的：运动作为一种非药物干预可以直接通过外泌体穿过血脑屏障发挥有益作用，减少脑缺血/再灌注损伤（CI/RI）后的细胞凋亡。miRNA-124 （miR-124）存在于外泌体中，在调节脑神经活动中起重要作用；然而，运动与CI/RI后外泌体活性和细胞凋亡之间的关系机制尚不清楚。因此，本研究从外泌体miR-124和细胞凋亡的角度探讨运动预处理对脑缺血再灌注损伤的影响。方法：通过阻断大鼠大脑中动脉建立大脑中动脉闭塞/再灌注（MCAO/R）模型，选择电动跑轮作为运动预处理方法，在6 h、12 h和24 h时间点检测外胞体样品的形态、颗粒浓度和粒径分布。采用RT-PCR、western blotting、免疫组化、TUNEL染色、TTC染色、mNSS评分等方法观察运动预处理对MCAO/R大鼠细胞凋亡的影响。结果：运动可减轻神经功能障碍和梗死面积，24 h时血浆外分泌miR-124含量增加，从而抑制STAT3的表达，增加抗凋亡BCL-2的表达，降低促凋亡BAX的表达，从而减少细胞凋亡。结论：运动预处理可通过外泌体miR-124、STAT3、BCL-2/BAX通路增强大鼠缺血半暗带组织抗凋亡能力，减少CI/RI后细胞凋亡。

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Exercise preconditioning increases circulating exosome miR-124 expression and alleviates apoptosis in rats with cerebral ischemia–reperfusion injury

Objectives

Exercise as a non-pharmacological intervention can exert beneficial effects directly through exosomes crossing the blood–brain barrier and reduce apoptosis after cerebral ischaemia/reperfusion injury (CI/RI). miRNA-124 (miR-124) is present in exosomes and plays an important role in regulating cerebral neurological activity; however, the mechanism of the relationship between exercise and the activity of exosomes and apoptosis after CI/RI remains unclear. Therefore, the present study investigated the effects of exercise preconditioning on CI/RI from the perspective of exosomal miR-124 and apoptosis.

Methods

The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by blocking the middle cerebral artery, and a motorized running wheel was chosen as the method of exercise preconditioning for rats, the morphology, particle concentration and particle size distribution of the exosome samples were identified at the 6 h, 12 h, and 24 h time points. RT-PCR, western blotting, immunohistochemistry, TUNEL staining, TTC staining and mNSS scores were used to investigate the effects of exercise preconditioning on apoptosis in MCAO/R rats.

Results

The results showed exercise reduced neurological dysfunction and infarct size, increased the content of plasma exocrine miR-124 at 24 h, which inhibited the expression of STAT3, increased the expression of the anti-apoptotic BCL-2, and decreased the expression of the pro-apoptotic BAX, thereby reducing apoptosis.

Conclusions

Our findings indicated that exercise preconditioning can enhance the anti-apoptotic capacity of tissues in the rat ischemic penumbra and reduce apoptosis after CI/RI via the exosomal miR-124, STAT3, BCL-2/BAX pathway.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.