MicroRNA-199a-5p attenuates blood-brain barrier disruption following ischemic stroke by regulating PI3K/Akt signaling pathway.

IF 2.9 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES PLoS ONE Pub Date : 2024-09-20 eCollection Date: 2024-01-01 DOI:10.1371/journal.pone.0306793

Guangxiao Ni, Lulu Kou, Chunqiao Duan, Ran Meng, Pu Wang

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Abstract

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.

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目的探讨缺血性脑卒中后miR-199a-5p是否通过PI3K/Akt通路调控BBB的完整性：方法：用成年雄性Sprague-Dawley大鼠进行永久性大脑中动脉闭塞（MCAO）实验。采用 Ludmila Belayev 12 点评分法测量 MCAO 大鼠的神经功能。结果表明，miR-199a-5p模拟物对大鼠MCAO后BBB完整性的影响是显著的：结果表明，miR-199a-5p模拟物具有提高MCAO大鼠本体感觉和运动活性的潜力。MiR-199a-5p可降低MCAO后PIK3R2的表达，激活Akt信号通路，并增加缺血半影中Claudin-5和VEGF的表达。此外，miR-199a-5p 还能减轻脑缺血后的炎症反应。用miR-199a-5p模拟物治疗的MCAO大鼠的BBB渗漏和神经细胞凋亡均有所减少：MiR-199a-5p模拟物降低了缺血性脑卒中后PIK3R2的表达和Akt信号通路的激活，减少了炎症细胞因子的表达，减轻了缺血性脑卒中后BBB的破坏。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS ONE 生物-生物学

CiteScore

6.20

自引率

5.40%

发文量

14242

审稿时长

3.7 months

期刊介绍： PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage