期刊
BRAIN RESEARCH
卷 1685, 期 -, 页码 9-18出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2018.01.036
关键词
Tongxinluo; MEK12ERK12p90RSK pathway; Bad protein; Cerebral ischemia and reperfusion injury; Neuroprotection
资金
- National Natural Science Foundation of China [81703857, 81703849, 81373866, 81173389, 81202813]
- Shanghai Key Disease Category Construction Projects of Chinese Integrative Medicine [zxbz2012-10]
- Three-year development plan project for Traditional Chinese Medicine [ZY3-CCCX-3-7003]
- Zhongshan Hospital [2015ZSYXQN28]
- Special fund for Standardized training of resident physicians in Zhongshan Hospital [008]
Ischernic stroke brings a huge family and social burden. Although the reperfusion of ischemic cerebral tissue is the most important way to rescue ischemic stroke, ischemia-reperfusion (I/R) injury further results in brain damage and even lead to death. Recent studies demonstrated that Tongxinluo (TXL) helps to protect the brain against focal cerebral I/R injury in rats by reducing neuronal apoptosis, and the MEK1/2/ERK1/2/90 ribosomal S6 kinase (p90RSK) pathway may be involved in this protective effect. Therefore, our present research was designed to identify the potential mechanisms involved. Adult male Sprague-Dawley rats (n = 108) were randomly divided into 4 groups: sham, cerebral ischemia and reperfusion (I/R), I/R plus TXL (TXL), and TXL plus U0126, a highly selective inhibitor of MEK 1 and MEK 2 (TXL + U0126). Brain edema was measured by T2-weighted magnetic resonance imaging (MRI). Pathological destruction of the blood brain barrier (BBB) ultrastructure was assessed by transmission electron microscopy, and proteins involved in the MEK1 /2/ERK1/2/p90RSK pathway were detected by immunofluorescence and Western blotting. Our results indicated that TXL significantly improved neurological function, reduced brain edema, ameliorated the destruction of the BBB ultrastructure and markedly reduced neuronal injury. However, these benefits were diminished when the MEK1 /2/ERK1/2/p90RSK pathway was inhibited by U0126. We also found that TXL upregulated the expression levels of p-MEK1 /2, p-ERK1 /2, p-p9ORSK and p-bad, which were all significantly reversed by U0126. Collectively, our data demonstrate that TXL provides neuroprotection against cerebral I/R injury and neuronal injury, and that these effects are mediated, in part, by activation of the MEK1/2/ERK1/2/p90RSK pathway. (C) 2018 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据