High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH
High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH
复制标题
高血清 MiR-130a 水平与严重血肿周围水肿相关，可预测急性脑出血的不良后果
DOI：
10.1007/s12035-015-9099-0
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发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Hu, Bo
中科院分区：
文献类型：
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作者：
Wang, Meng-Die;Wang, Yong;Hu, Bo
急性自发性脑出血（ICH）患者血肿周围水肿（PHE）的发生和/或进展因个体而异。虽然血肿体积是预测PHE的一个有用指标，但在ICH早期，其预测能力并不好。迫切需要更好的预测器。在这项研究中，我们发现miR-130 a在ICH患者血清中升高，并且是发病后前3天内与PHE体积正相关的独立指标。结合血肿块进一步评价R2。仅在深部血肿患者中，血清miR-130 a水平与临床结局（第14天的美国国立卫生研究院卒中量表（NIHSS）评分和第90天的改良兰金量表（mRS）评分）相关。此外，miR-130 a在大鼠血清和血肿周围组织中显著增加，并且与脑水肿的变化一致。miR-130 a抑制剂减少脑水肿、血脑屏障（BBB）渗透性和增加神经功能缺损评分，并且miR-130 a模拟增加单层渗透性。凝血酶刺激的脑微血管内皮细胞（BMEC）是脑出血时miR-130 a的主要来源。在实验模型中，miR-130 a水平升高伴随着小窝蛋白-1降低和基质金属蛋白酶（MMP）-2/9增加。同时，小凹蛋白-1（cav-1）被miR-130 a模拟物减少，伴随着MMP-2/9表达的增加。上调的MMP-2/9然后下调cavtratin，cav-1支架结构域肽。这种调节机制在凝血酶诱导的细胞ICH模型中得到验证。我们的研究结果表明，血清miR-130 a可能作为一个有用的早期生物标志物监测ICH后PHE和预测预后，可能有助于个体化治疗的决策。
The development and/or progression of perihematomal edema (PHE) in patients with acute spontaneous intracerebral hemorrhage (ICH) vary substantially with different individuals. Although hematoma volume is a useful indicator for predicting PHE, its predictive power was not good at the early stage of ICH. Better predictors are urgently needed. In this study, we found that miR-130a was elevated in the serum of ICH patients and was an independent indicator positively associated with PHE volume within the first 3 days after onset. TheR2was further evaluated when it is used in combination with hematoma mass. Serum miR-130a levels were associated with clinical outcome (National Institute of Health Stroke Scale (NIHSS) scores at day 14 and modified Rankin Scale (mRS) scores at day 90) only in patients with deep hematoma. Moreover, miR-130a was significantly increased in rat serum and perihematomal tissues and was in line with the change in brain edema. MiR-130a inhibitors reduced brain edema, blood–brain barrier (BBB) permeability, and increased neurological deficit scores, and miR-130a mimics increased monolayer permeability. Thrombin-stimulated brain microvascular endothelial cells (BMECs) were a main source of miR-130a under ICH. In the experimental model, the elevated miR-130a level was accompanied by the decreased caveolin-1 and increased matrix metalloproleinase (MMP)-2/9. Meanwhile, caveolin-1 (cav-1) was reduced by miR-130a mimics, accompanied by an increase in MMP-2/9 expression. The upregulated MMP-2/9 was then downregulated by cavtratin, a cav-1 scaffolding domain peptide. This regulation mechanism was authenticated in a thrombin-induced cellular ICH model. Our results suggest that serum miR-130a may serve as a useful early biomarker for monitoring post-ICH PHE and predicting prognosis and may be helpful in the decision-making of individualized therapy.