微小 RNA-199a-5p 通过调控 PI3K/Akt 信号通路减轻缺血性脑卒中后血脑屏障破坏。
MicroRNA-199a-5p attenuates blood-brain barrier disruption following ischemic stroke by regulating PI3K/Akt signaling pathway.
机构信息
Department of Rehabilitation of the Second Hospital of Hebei Medical University, Shijiazhuang, China.
Stomatological Laboratory of the Second Hospital of Hebei Medical University, Shijiazhuang, China.
出版信息
PLoS One. 2024 Sep 20;19(9):e0306793. doi: 10.1371/journal.pone.0306793. eCollection 2024.
OBJECTIVE
To explore whether miR-199a-5p regulated BBB integrity through PI3K/Akt pathway after ischemia stroke.
METHODS
Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion(MCAO) were used in experiment. The Ludmila Belayev 12-point scoring was used to measure the neurological function of MCAO rats. The Evans Blue Stain, immunofluorescence staining, western-blotting and RT-PCR were performed to evaluate the effects of miR-199a-5p mimic on BBB integrity in rats following MCAO.
RESULTS
The result suggested that miR-199a-5p mimic treatment possessed the potential to boost proprioception and motor activity of MCAO rats. MiR-199a-5p decreased the expression of PIK3R2 after MCAO, activated Akt signaling pathway, and increased the expression of Claudin-5 and VEGF in the ischemic penumbra. Furthermore, miR-199a-5p alleviated inflammation after cerebral ischemia. BBB leakage and neurocyte apoptosis were cut down in MCAO rats treated with miR-199a-5p mimic.
CONCLUSIONS
MiR-199a-5p mimic decreased the expression of PIK3R2 and activated Akt signaling pathway after ischemia stroke, reduced the expression of inflammatory cytokines, and attenuated BBB disruption after ischemic stroke.
目的
探讨 miR-199a-5p 是否通过 PI3K/Akt 通路调节缺血性脑卒中后血脑屏障的完整性。
方法
采用成年雄性 Sprague-Dawley 大鼠永久性大脑中动脉闭塞（MCAO）模型进行实验。采用 Ludmila Belayev 12 分评分法评估 MCAO 大鼠的神经功能。通过伊文思蓝染色、免疫荧光染色、Western-blotting 和 RT-PCR 检测 miR-199a-5p 模拟物对 MCAO 大鼠血脑屏障完整性的影响。
结果
结果表明，miR-199a-5p 模拟物处理具有增强 MCAO 大鼠本体感觉和运动活动的潜力。miR-199a-5p 降低了 MCAO 后 PIK3R2 的表达，激活了 Akt 信号通路，并增加了缺血半影区 Claudin-5 和 VEGF 的表达。此外，miR-199a-5p 减轻了脑缺血后的炎症反应。MCAO 大鼠给予 miR-199a-5p 模拟物后，BBB 渗漏和神经细胞凋亡减少。
结论
miR-199a-5p 模拟物降低了缺血性脑卒中后 PIK3R2 的表达并激活了 Akt 信号通路，减少了炎症细胞因子的表达，并减轻了缺血性脑卒中后 BBB 的破坏。
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