医学
血脑屏障
蛋白激酶B
脑出血
血管通透性
药理学
PI3K/AKT/mTOR通路
血管内皮生长因子
炎症
下调和上调
水肿
标记法
血管生成
细胞凋亡
麻醉
病理
癌症研究
免疫学
化学
中枢神经系统
内分泌学
内科学
蛛网膜下腔出血
免疫组织化学
血管内皮生长因子受体
基因
生物化学
作者
Tianyang Xi,Feng Jin,Ying Zhu,Jialu Wang,Ling Tang,Yanzhe Wang,David S Liebeskind,Zhiyi He
标识
DOI:10.1016/j.bbrc.2017.10.064
摘要
MiR-126, a microRNA implicated in blood vessel integrity, angiogenesis and vascular inflammation, is markedly decreased in the sera of patients with intracerebral hemorrhage (ICH). The current study aims to evaluate the potential therapeutic effect of miR-126-3p on brain injuries in a rat model of collagenase-induced ICH. Intracerebroventricular administration of a miR-126-3p mimic significantly alleviated behavioral defects 24 h after ICH, as examined by paw placement and corner tests. ICH led to increased blood-brain barrier (BBB) permeability and cerebral edema, both of which were attenuated by miR-126-3p mimic. Treatment with miR-126-3p mimic reduced the numbers of myeloperoxidase (MPO)-positive, OX42-positive, Fluoro Jade B (FJB)-positive and NEUN/TUNEL double-positive cells around the hematoma, implying that miR-126-3p inhibited neutrophil infiltration, microglial activation and neuronal apoptosis following hemorrhage. In addition, miR-126-3p mimic suppressed the upregulation of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) in the perihematomal area and maintained the activation of Akt. Furthermore, in vitro assays confirmed upregulation of PIK3R2 upon knockdown of miR-126-3p in rat brain microvascular endothelial cells (BMECs), and silencing of miR-126-3p resulted in impaired BMEC barrier permeability and reversed vascular endothelial growth factor (VEGF)- and angiopoietin-1 (Ang-1)-induced activation of Akt and inhibition of BMEC apoptosis. In summary, our results suggest that exogenous miR-126-3p may alleviate BBB disruption, cerebral edema and neuronal injury following ICH by targeting PIK3R2 and the Akt signaling pathway in brain vascular endothelium.
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