Beneficial effect of magnesium lithospermate B on cerebral ischemia-reperfusion injury in rats involves the regulation of miR-107/glutamate transporter 1 pathway
Beneficial effect of magnesium lithospermate B on cerebral ischemia-reperfusion injury in rats involves the regulation of miR-107/glutamate transporter 1 pathway
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紫精酸镁 B 对大鼠脑缺血再灌注损伤的有益作用涉及 miR-107/谷氨酸转运蛋白 1 通路的调节
DOI：
10.1016/j.ejphar.2015.09.042
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发表时间：
2015-11-05
影响因子：
5
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Yang, Zhong-Bao;Luo, Xiu-Ju;Peng, Jun
近年来的研究发现，脑缺血再灌注后谷氨酸蓄积与miR-107/谷氨酸转运体-1(GLT-1)通路功能障碍有关，紫草酸镁B(MLB)具有抗兴奋性毒性的药理活性。本研究旨在探讨延胡索乙素能否通过调节miR-107/GLT-1通路对L再灌注大鼠的兴奋性神经毒性起到保护作用。大鼠脑缺血2 h再灌注24 h建立脑I/R损伤模型，神经功能评分增加，脑梗塞体积增加，细胞凋亡增加，伴有谷氨酸积聚，miR-107升高，GLT-1表达下调。给予MLB可减轻脑I/R损伤，并逆转谷氨酸蓄积、miR-107和GLT-1的表达。接下来，我们在神经细胞缺氧/复氧(H/R)损伤模型中研究了MLB与miR-107/GLT-1通路的关系。H/R处理增加神经细胞凋亡伴随谷氨酸蓄积和miR-107升高，并抑制GLT-1的表达，这与我们在体内的研究结果相似。这些作用在MLB的存在下被逆转，证实MLB与miR-107/GLT-1通路有很强的相关性。因此，我们认为MLB通过调节miR-107/GLT-1通路对大鼠脑I/R兴奋性神经毒性具有保护作用。(C)2015爱思唯尔B.V.保留所有权利。
Recent studies uncovered that glutamate accumulation following cerebral ischemia-reperfusion (I/R) was related to the dysfunction of miR-107/glutamate transporter-1(GLT-1) pathway and magnesium lithospermate B (MLB) possesses the pharmacological activity of anti-excitotoxicity. This study aims to explore whether MLB is able to protect rat brain from excitatory neurotoxicity during l/R by modulating miR-107/GLT-1 pathway. Rats were subjected to 2 h of cerebral ischemia following by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score, infarct volume and cellular apoptosis concomitant with glutamate accumulation, miR-107 elevation and GLT-1 downregulation. Administration of MLB reduced I/R-induced cerebral injury accompanied by a reverse in glutamate accumulation, miR-107 and GLT-1 expression. Next, we examined the association of MLB with miR-107/GLT-1 pathway in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased the nerve cells apoptosis concomitant with glutamate accumulation and miR-107 elevation, and suppressed GLT-1 expression, mimicking our in vivo findings. All these effects were reversed in the presence of MLB, confirming a strong correlation between MLB and miR-107/GLT-1 pathway. Based on these observations, we conclude that MLB is able to protect the rat brain from excitatory neurotoxicity during I/R through the regulation of miR-107/GLT-1 pathway. (C) 2015 Elsevier B.V. All rights reserved.