Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina
Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina
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DOI：
10.1016/j.exer.2011.07.003
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Peng, Yi-Hao
中科院分区：
文献类型：
--
作者：
Ko, Mei-Lan;Chen, Chau-Fong;Peng, Yi-Hao
辛伐他汀已被证明可以通过介导应激蛋白的表达来增强缺血再灌注 (IR) 损伤后视网膜神经节细胞 (RGC) 的存活率。本研究的目的是研究辛伐他汀对大鼠 IR 模型中视网膜神经元和凋亡蛋白表达的影响。 Wistar大鼠视网膜再灌注后立即接受玻璃体内注射辛伐他汀。通过将眼内压增加至 150 mmHg 60 分钟来诱导视网膜缺血。用氟金逆行标记后测量存活 RGC 的数量。使用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 研究缺血诱导的细胞凋亡。我们发现辛伐他汀治疗可使视网膜缺血后 RGC 存活率提高约 40%，并减少视网膜神经元凋亡。通过蛋白质印迹分析，我们发现辛伐他汀上调了视网膜中 Bcl-2 的表达。相反，Bax 蛋白的水平不受辛伐他汀治疗的影响。我们的结果表明，辛伐他汀可以预防视网膜 IR 引起的 RGC 损失，并且该过程的机制可能涉及细胞凋亡途径的改变。 (C) 2011 Elsevier Ltd. 保留所有权利。
Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. The purpose of this study was to investigate the effect of simvastatin on retinal neurons and the expression of apoptotic proteins in a rat IR model. Wistar rats received intravitreal injection of simvastatin immediately after retinal reperfusion. Retinal ischemia was induced by increasing intraocular pressure to 150 mmHg for 60 min. The number of viable RGCs was measured after retrograde labeling with Fluoro-Gold. Ischemia-induced apoptotic cell death was studied using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). We found that simvastatin treatment enhanced RGC survival after retinal ischemia by approximately 40% and decreased retinal neuronal apoptosis. Using western blot analysis, we found that simvastatin upregulated the expression of Bcl-2 in the retina. In contrast, the level of the protein Bax was unaffected by simvastatin treatment. Our results suggest that RGC loss induced by retinal IR may be prevented by simvastatin and that the mechanism underlying this process possibly involves an alteration in the apoptotic pathway. (C) 2011 Elsevier Ltd. All rights reserved.